Perinatal Institute

Neonatal chronic lung disease; late preterm infant

MD: University of Illinois College of Medicine, Chicago, IL, 1977-1981.

Pediatric Internship and Residency: University of Minnesota Hospital and Clinic, Minneapolis, MN, 1981-1984. Chief Resident, Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1984.

Fellowship: Immunology/Neonatology, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1985-1987; 1988-1989; visiting scientist, Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, England.

Certification: American Board of Pediatrics, 1988; subspecialty board, Neonatal/Perinatal Medicine, 1989.

Binder S, Hill K, Meinzen-Derr J, Greenberg JM, Narendran V. Increasing VLBW Deliveries at Subspecialty Perinatal Centers via Perinatal Outreach. Pediatrics. 2011 Mar;127(3):487-93.

Kulkarni RM, Herman A, Ikegami M, Greenberg JM, Akeson AL. Lymphatic ontogeny and effect of hypoplasia in developing lung. Mech Dev. 2011 Jan-Feb;128(1-2):29-40.

Kulkarni RM, Greenberg JM, Akeson AL. NFATc1 regulates lymphatic endothelial development. Mech Dev. 2009 May-Jun;126(5-6):350-65.

Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.

Preciado DA, Rutter MJ, Greenberg JM, Bahado-Singh R, Lambers D, Willging JP. Intrapartum management of severe fetal airway obstruction. J Otolaryngol. 2004 Oct;33(5):283-8.

Akeson AL, Cameron JE, Le Cras TD, Whitsett JA, Greenberg JM. Vascular endothelial growth factor-A induces prenatal neovascularization and alters bronchial development in mice. Pediatr Res. 2005 Jan;57(1):82-8.

Greenberg JM, Thompson FY, Brooks SK, Shannon JM, Akeson AL. Slit and robo expression in the developing mouse lung. Dev Dyn. 2004 Jun;230(2):350-60.

Le Cras TD, Spitzmiller RE, Albertine KH, Greenberg JM, Whitsett JA, Akeson AL. VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. Am J Physiol Lung Cell Mol Physiol. 2004 Jul;287(1):L134-42.

Akeson AL, Greenberg JM, Cameron JE, Thompson FY, Brooks SK, Wiginton D, Whitsett JA. Temporal and spatial regulation of VEGF-A controls vascular patterning in the embryonic lung. Dev Biol. 2003 Dec 15;264(2):443-55.

Greenberg JM, Thompson FY, Brooks SK, Shannon JM, McCormick-Shannon K, Cameron JE, Mallory BP, Akeson AL. Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung. Dev Dyn. 2002 Jun;224(2):144-53.

Louis J. Muglia, MD, PhD Co-Director, Perinatal Institute

is a pediatric endocrinologist whose research efforts seek to define the mechanisms controlling the timing for birth in humans to prevent or better treat human preterm labor. Recent efforts analyze the contribution of genetic determinants to preterm birth. A second area of investigation is elucidation of the molecular pathways involved in the behavioral and neuroendocrine responses to stress.
Visit the Muglia Lab.

513-803-7902 louis.muglia@cchmc.org

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Louis J. Muglia, MD, PhD

Co-Director, Perinatal Institute

Director, Center for Prevention of Preterm Birth

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-7902

Email louis.muglia@cchmc.org

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Pediatric endocrinology

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Biography

Dr. Muglia has pioneered the in vivo analyses of regulation of the endocrine stress response and the molecular pathways leading to birth using novel genetically altered mutant mice. These studies have elucidated the importance of corticotropin-releasing hormone, glucocorticoids, and prostaglandins in neuroendocrine modulation, behavior, and perinatal adaptation. These studies have evolved over the last decade to specifically focus on the mechanisms controlling the timing for birth in humans using genetics and comparative genomics. The composition of the biological clock metering the duration of human gestation remains a central question in reproductive biology. The goal of the Muglia Laboratory is to understand the molecular timing machinery comprising this biological clock to prevent or better treat human preterm labor and delivery.

Among Dr. Muglia’s achievements are more than 180 publications and many awards, including a Burroughs Wellcome Fund Career Development Award in the biomedical sciences, the Society of Pediatric Research Young Investigator Award, and election to the American Society for Clinical Investigation and Association of American Physicians. In 2010, Dr. Muglia was elected to fellow in the American Association for the Advancement of Science. He is an active member of the Society for Pediatric Research, Society for Neuroscience, and the Lawson Wilkins Pediatric Endocrine Society. Dr. Muglia currently serves as chair of the Board of Scientific Counselors for the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. In 2013, Dr. Muglia was elected to membership in the Institute of Medicine of the National Academies.

BS: University of Michigan, Ann Arbor, MI, 1981.

PhD: University of Chicago, Chicago, IL, 1986.

MD: University of Chicago, Chicago, IL, 1988.

Plunkett J, Doniger S, Orabona G, Morgan T, Haataja R, Hallman M, Puttonen H, Menon R, Kuczynski E, Norwitz E, Victoria Snegovskikh V, Palotie A, Peltonen L, Fellman V, DeFranco EA, Chaudhari BP, McGregor TL, McElroy JJ, Oetjens MT, Teramo K, Boreck I, Fay J, Muglia L. An evolutionary genomic approach to identify genes involved in human birth timing. PLoS Genetics. 2011; 7: e1001365.

Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010; 362: 529-535.

Kolber BJ, Boyle MP, Wieczorek L, Kelley CL, Kelley CL, Onwuzurike CC, Nettles SA, Vogt SK, Muglia LJ. Transient early-life forebrain corticotropin-releasing hormone elevation causes long-lasting anxiogenic and despair-like changes in mice. J Neurosci. 2010; 30: 2571-2581.

Plunkett J, Feitosa MF, Trusgnich M, Wangler MF, Palomar L, Kistka ZA-F, DeFranco EA, Shen TT, Stormo EAD, Puttonen H, Hallman M, Haataja R, Luukkonen A, Fellman V, Peltonen L, Palotie A, Daw EW, An P, Teramo K, Borecki I, Muglia LJ. Mother’s genome or maternally-inherited genes acting in the fetus influence gestational age in familial preterm birth. Human Heredity. 2009; 68: 209-219.

Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ. Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci USA. 2008; 105: 12004 - 12009.

Roizen J, Asada M, Tong M, Tai H-H, Muglia LJ. Preterm birth without progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. Mol Endocrinol. 2008; 22: 105-112.

Kistka Z A-F, Palomar P, Lee KA, Boslaugh SE, Wangler MF, Cole FS, DeBaun MR, Muglia LJ. Racial disparity in the frequency of recurrence of preterm birth. Am J Obstet Gynecol. 2007; 196: 131.e1-131.e6.

Bethin KE, Nagai Y, Sladek R, Asada M, Sadovsky Y, Hudson TJ, Muglia LJ. Microarray analysis of uterine gene expression in mouse and human pregnancy. Mol Endocrinol. 2003; 17: 1454-1469.

Gross G, Imamura T, Luedke C, Vogt SK, Olson LM, Nelson DM, Sadovsky Y, Muglia LJ. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Proc. Natl. Acad. Sci. USA. 1998; 95: 11871-11875.

Muglia LJ, Jacobson L, Dikkes P, Majzoub JA. Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature. 1995; 373:427-432.

Grants

Maternal Temperament, Stress, Inflammation and Preterm Birth. Multi-PI. NIH/NICHD. Sep 2013-Aug 2017.

March of Dimes Prematurity Research Center Ohio Collaborative. Coordinating PI. March of Dimes. Jul 2013-Jun 2018.

Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute

investigates the hierarchy of transcriptional controls and signaling cascades which determine commitment of progenitor cells that produce the differentiated epithelial cells lining the primordial and mature respiratory tract. The goal of his research is to provide insight into the pathogenesis of acute and chronic lung disorders. The role of surfactant in innate host defense and lung function is also an ongoing interest.
Visit the Whitsett Lab.

513-803-2790 jeffrey.whitsett@cchmc.org

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Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy

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Biography

Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.

Dr. Whitsett received his medical degree from Columbia University, in New York, and has been a faculty member since 1977. He is internationally known for his research in pulmonary medicine, as well as for his clinical expertise in neonatology.

Dr. Whitsett has made a series of groundbreaking contributions in pulmonary medicine. His major pioneering work has been on surfactant proteins A, B, C and D, cloning their genes, and clarifying their roles in lung development.

Throughout his career, Dr. Whitsett has had the remarkable ability to move from molecular biology, to animal models, to diagnosis and therapy of human disease. He played a critical role in making surfactant protein replacement a routine tool for treating immature lungs and respiratory distress syndrome in premature infants. His laboratory has contributed to the identification of a number of genes critical for lung formation and function. Mutations in genes regulating surfactant homeostasis were shown to cause acute and chronic lung disease in infants and adults.

Dr. Whitsett is a member of the Institute of Medicine, National Academy of Sciences and is the recipient of the Mead Johnson Award, a National Institutes of Health (NIH) Merit Award, the first Julius Comroe Lectureship in Pulmonary Research from FASEB, the William Cooper Procter Award from Cincinnati Children's, the Amberson Lecture Award of the American Thoracic Society, the prestigious Daniel Drake Medal for scientific contributions from the University of Cincinnati College of Medicine, the International Arvo Ylppö Medal from the Finnish Foundation for Pediatric Research and the Grand Hamdan International Award on Neonatal Medicine from the United Arab Emirates.

Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.

MD: Columbia University, New York, NY, 1973.

Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.

Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.

Sivaprasad U, Askew DJ, Ericksen MB, Gibson AM, Stier MT, Brandt EB, Bass SA, Daines MO, Chakir J, Stringer KF, Wert SE, Whitsett JA, Le Cras TD, Wills-Karp M, Silverman GA, Khurana Hershey GK. A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6.

Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.

Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1292-304.

Wang IC, Zhang Y, Snyder J, Sutherland MJ, Burhans MS, Shannon JM, Park HJ, Whitsett JA, Kalinichenko VV. Increased expression of FoxM1 transcription factor in respiratory epithelium inhibits lung sacculation and causes Clara cell hyperplasia. Dev Biol. 2010 Nov 15;347(2):301-14.

Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.

Tompkins DH, Besnard V, Lange AW, Keiser AR, Wert SE, Bruno MD, Whitsett JA. Sox2 Activates Cell Proliferation and Differentiation in the Respiratory Epithelium. Am J Respir Cell Mol Biol. 2010 Sep 20.

Meyer SE, Hasenstein JR, Baktula A, Velu CS, Xu Y, Wan H, Whitsett JA, Gilks CB, Grimes HL. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. Am J Pathol. 2010 Sep;177(3):1503-13.

Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.

Sakagami T, Beck D, Uchida K, Suzuki T, Carey BC, Nakata K, Keller G, Wood RE, Wert SE, Ikegami M, Whitsett JA, Luisetti M, Davies S, Krischer JP, Brody A, Ryckman F, Trapnell BC. Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. Am J Respir Crit Care Med. 2010 Jul 1;182(1):49-61.

Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.

Division Head

Emeritus

James L. Lessard, PhD

assesses the functional and developmental significance of the four distinct forms of muscle actins. His lab also studies the regulation of visceral smooth muscle growth and differentiation.

513-636-8308 james.lessard@cchmc.org

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James L. Lessard, PhD

Academic Affiliations

Emeritus, UC Department of Pediatrics

Phone 513-636-8308

Fax 513-636-4317

Email james.lessard@cchmc.org

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Gene regulation; gene targeting

PhD: Marquette University, Milwaukee, Wisc., 1970.

Ustiyan V, Wang IC, Ren X, Zhang Y, Snyder J, Xu Y, Wert SE, Lessard JL, Kalin TV, Kalinichenko VV. Forkhead box M1 transcriptional factor is required for smooth muscle cells during embryonic development of blood vessels and esophagus. Dev Biol. 2009 Dec 15;336(2):266-79.

Kumar A, Crawford K, Flick R, Klevitsky R, Lorenz JN, Bove KE, Robbins J, Lessard JL. Transgenic overexpression of cardiac actin in the mouse heart suggests coregulation of cardiac, skeletal and vascular actin expression. Transgenic Res. 2004 Dec;13(6):531-40.

Szucsik JC, Lewis AG, Marmer DJ, Lessard JL. Urogenital tract expression of enhanced green fluorescent protein in transgenic mice driven by a smooth muscle gamma-actin promoter. J Urol. 2004 Feb;171(2 Pt 1):944-9.

Crawford K, Flick R, Close L, Shelly D, Paul R, Bove K, Kumar A, Lessard J. Mice lacking skeletal muscle actin show reduced muscle strength and growth deficits and die during the neonatal period. Mol Cell Biol. 2002 Aug;22(16):5887-96.

Qian J, Hendrix M, Larsen WJ, Dorn GW 2nd, Lessard JL. Establishment and characterization of a conditionally immortalized smooth muscle/myometrial-like cell line. Mol Reprod Dev. 1997 Jul;47(3):284-94.

Kumar A, Crawford K, Close L, Madison M, Lorenz J, Doetschman T, Pawlowski S, Duffy J, Neumann J, Robbins J, Boivin GP, O'Toole BA, Lessard JL. Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4406-11.

Ng WA, Doetschman T, Robbins J, Lessard JL. Muscle isoactin expression during in vitro differentiation of murine embryonic stem cells. Pediatr Res. 1997 Feb;41(2):285-92.

Qian J, Kumar A, Szucsik JC, Lessard JL. Tissue and developmental specific expression of murine smooth muscle gamma-actin fusion genes in transgenic mice. Dev Dyn. 1996 Oct;207(2):135-44.

Szucsik JC, Lessard JL. Cloning and sequence analysis of the mouse smooth muscle gamma-enteric actin gene. Genomics. 1995 Jul 20;28(2):154-62.

Sawtell NM, Hartman AL, Lessard JL. Conserved tissue-restricted expression of HUC 1-1 actin phenotype among eumetazoan organisms. J Exp Zool. 1990 Oct;256(1):54-62.

William J. Scott, DVM, PhD

focuses on the effects of human teratogens in rodents; specifically, the pattern formation along the anterior (thumb) / posterior (pinky) axis affected by drug exposure.

513-636-8173 william.scott@cchmc.org

Dan Wiginton, PhD

uses transgenic and gene knockout mouse models to investigate in vivo mechanisms of gene regulation during cell differentiation and tissue development, with current focus on the intestinal epithelium. Special interest is the role of Onecut factors in intestinal development and function.
Visit the Wiginton Lab.

513-636-4547 dan.wiginton@cchmc.org

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Dan Wiginton, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-4547

Fax 513-636-4317

Email dan.wiginton@cchmc.org

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Clinical

Gene regulation and development; regulatory factor networks; enhancers; chromatin modulation

Research

Visit the Wiginton Lab.

Biography

Dan Wiginton, PhD, has been in the Department of Pediatrics at Children's Hospital and the University of Cincinnati since 1984. The principal focus of his work during that time has been basic research and research training of graduate students and postdoctoral fellows. Dr. Wiginton's current research interests are directed toward an understanding of the genetic regulatory networks that govern tissue and organ development, as well as the cell-type specific differentiation that underlies this development.

Dr. Wiginton's lab uses the human adenosine deaminase (ADA) gene as a model system to investigate tissue-specific gene expression and the mechanisms that govern it. Transgenic mouse technology has been utilized heavily in these studies, allowing investigation of these questions in vivo. With the ADA model, studies have been carried out to understand thymocyte differentiation in thymus (critical to development of the immune system) and epithelial development in small intestine (critical to normal nutrient utilization).

Prior to coming to Cincinnati, Dr. Wiginton carried out postdoctoral training at the University of Kentucky in Lexington and at the University of Texas Health Sciences Center in San Antonio under Dr. John Hutton. While at these institutions, Dr. Wiginton's research focused on characterization of the normal human ADA protein and gene, and defects in ADA structure and function that cause severe combined immunodeficiency disease (SCID). These studies included collaborations in very early studies directed toward stem cell gene therapy to correct ADA-deficient SCID. Dr. Wiginton carried out his graduate studies at the University of Texas (Austin) under Dr. William Shive. He was awarded a PhD in biochemistry in 1978, for studies in the area of bacterial enzyme expression and regulation. These studies investigated the biosynthesis and intermediary metabolism of the branched-chain amino acids (valine/leucine/isoleucine).

PhD: The University of Texas at Austin, 1978.

Postdoctoral Fellowship: University of Kentucky, Lexington, KY, 1978-1980.

Fellow / Chemist: Dept. of Hematology, UTHSC-San Antonio and Audie Murphy VA Hospital, San Antonio, TX, 1980-1984.

Dusing MR, Maier EA, Aronow BJ, Wiginton DA. Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine. Physiol Genomics. 2010 Jun;42(1):115-25.

Akeson A, Herman A, Wiginton D, Greenberg J. Endothelial cell activation in a VEGF-A gradient: relevance to cell fate decisions. Microvasc Res. 2010 Jul;80(1):65-74.

Maier EA, Dusing MR, Wiginton DA. Temporal regulation of enhancer function in intestinal epithelium: a role for Onecut factors. J Biol Chem. 2006 Oct 27;281(43):32263-71.

Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.

Faculty

Bruce J. Aronow, PhD Co-director, Computational Medicine Center

works toward unraveling both the role and mechanism by which the functional capabilities of the human genome shape human health and our ability to adapt to stressful challenges. The lab’s current research focus is to find or support efforts to solve problems relevant to genomic medicine by developing, both independently and collaboratively, new algorithms, tools and methodologies in translational bioinformatics.
Visit the Aronow/Jegga Lab.

513-636-0263 bruce.aronow@cchmc.org

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Bruce J. Aronow, PhD

Co-director, Computational Medicine Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-0263

Fax 513-636-2056

Email bruce.aronow@cchmc.org

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Visit the Aronow-Jegga Lab.

Biography

Dr. Aronow works toward unraveling both the role and mechanism by which the functional capabilities of the human genome shape human health and our ability to adapt to stressful challenges. The Aronow Lab focuses on collaborative research projects and the development of informatics systems that leverage multiple disciplines of knowledge, expertise and diverse data. The goal is to improve our collective ability to formulate high-impact inferences, hypotheses and next-stage experiments that could have the highest overall impact for biomedical research. The lab’s current research focus is to find or support efforts to solve problems relevant to genomic medicine by developing, both independently and collaboratively, new algorithms, tools and methodologies in translational bioinformatics. Dr. Aronow is also the first recipient of the John S. Hutton, MD, Chair for Biomedical Informatics.

BS: Chemistry, Stanford University, Stanford, CA, 1976.

PhD: Biochemistry, University of Kentucky, Lexington, KY, 1986.

Research Fellowship: Division of Basic Science Research, Cincinnati Children's Research Foundation, Cincinnati, OH, 1986-1989.

View Publications on Google Scholar

Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, Jegga AG, Aronow BJ, Lee CK, Bernard A, Glasser MF, Dierker DL, Menche J, Szafer A, Collman F, Grange P, Berman KA, Mihalas S, Yao Z, Stewart L, Barabási AL, Schulkin J, Phillips J, Ng L, Dang C, Haynor DR, Jones A, Van Essen DC, Koch C, Lein E. Canonical genetic signatures of the adult human brain. Nat Neurosci. 2015 Dec;18(12):1832-44.

Adams AK, Bolanos LC, Dexheimer PJ, Karns RA, Aronow BJ, Komurov K, Jegga AG, Casper KA, Patil YJ, Wilson KM, Starczynowski DT, Wells SI. IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival. Oncotarget. 2015 Oct 26.

Unruh D, Srinivasan R, Benson T, Haigh S, Coyle D, Batra N, Keil R, Sturm R, Blanco V, Palascak M, Franco RS, Tong W, Chatterjee T, Hui DY, Davidson WS, Aronow BJ, Kalfa T, Manka D, Peairs A, Blomkalns A, Fulton DJ, Brittain JE,
Weintraub NL, Bogdanov VY. Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis. Circulation. 2015 Nov 17;132(20):1898-908.

Chen S, Brunskill EW, Potter SS, Dexheimer PJ, Salomonis N, Aronow BJ, Hong CI, Zhang T, Kopan R. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan. Dev Cell. 2015 Oct 12;35(1):49-62.

Pfluger PT, Kabra DG, Aichler M, Schriever SC, Pfuhlmann K, García VC, Lehti M, Weber J, Kutschke M, Rozman J, Elrod JW, Hevener AL, Feuchtinger A, Hrabě de Angelis M, Walch A, Rollmann SM, Aronow BJ, Müller TD, Perez-Tilve D, Jastroch M, De Luca M, Molkentin JD, Tschöp MH. Calcineurin Links Mitochondrial Elongation with Energy Metabolism. Cell Metab. 2015 Nov 3;22(5):838-50.

Mrug M, Zhou J, Yang C, Aronow BJ, Cui X, Schoeb TR, Siegal GP, Yoder BK, Guay-Woodford LM. Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse. PLoS One. 2015 Aug 21;10(8):e0135678.

Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, Wellendorf AM, Valencia CA, Paddison PJ, Horwitz MS, Grimes HL, Lutzko C, Cancelas JA. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent
stem cells. J Clin Invest. 2015 Aug 3;125(8):3103-16.

Matrka MC, Hennigan RF, Kappes F, DeLay ML, Lambert PF, Aronow BJ, Wells SI. DEK over-expression promotes mitotic defects and micronucleus formation. Cel Cycle. 2015 May 6:1-15.

Sayed N, Wong WT, Ospino F, Meng S, Lee J, Jha A, Dexheimer P, Aronow BJ, Cooke JP. Transdifferentiation of human fibroblasts to endothelial cells: role of innate immunity. Circulation. 2015 Jan 20;131(3):300-9.

Chang KH, Sengupta A, Nayak RC, Duran A, Lee SJ, Pratt RG, Wellendorf AM, Hill SE, Watkins M, Gonzalez-Nieto D, Aronow BJ, Starczynowski DT, Civitelli R, Diaz-Meco MT, Moscat J, Cancelas JA. p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche. Cell Rep. 2014 Dec 24;9(6):2084-97.

Samantha A. Brugmann, PhD Member, Division of Plastic Surgery

is a developmental biologist who aims to understand craniofacial development and elucidate the molecular basis for diseases that affect the craniofacial complex. Furthermore, Dr. Brugmann attempts to understand the forces that help pattern the face during normal and abnormal development she utilizes various model systems with unique facial morphologies.

Visit the Brugmann Lab.

513-636-7678 samantha.brugmann@cchmc.org

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Samantha A. Brugmann, PhD

Member, Division of Plastic Surgery

Academic Affiliations

Assistant Professor, UC Department of Surgery

Phone 513-636-7678

Email samantha.brugmann@cchmc.org

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Craniofacial development

Visit the Brugmann Lab.

Biography

Samantha A. Brugmann, PhD, is an assistant professor of pediatrics in the Divisions of Plastic Surgery and Developmental Biology within the University of Cincinnati College of Medicine. She received her BS in cell and molecular biology from Tulane University in New Orleans, LA. She then obtained her PhD in genetics from George Washington University in Washington, DC where she studied cranial sensory placode development in Xenopus laevis. She performed her postdoctoral fellowship at Stanford University where her research focused on craniofacial development. While at Stanford she received a Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (F32), a Pediatric Research Fund-Child Health Research Program Grant and a NIH Pathway to Independence Award (K99/R00). She joined Cincinnati Children’s Hospital Medical Center in January 2011 to study craniofacial development and disease.

BS: Tulane University, New Orleans, LA.

PhD: George Washington University, Washington DC.

Fellowship: Stanford University, Stanford, CA.

Chang CF, Schock EN, Attia A, Stottmann RW, Brugmann SA. The ciliary baton: orchestrating neural crest development. Current Topics in Developmental Biology. In press.

Brugmann SA, Wells JM. Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res Ther. 2013;4 Suppl 1:S1.

Liu H, Lan Y, Xu , Chang CF, Brugmann SA, Jiang R. Odd-skipped related-1 controls neural crest chondrogenesis during tongue development. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18555-60.

Chang CF, Schock EN, O’Hare EA, Dodgson J, Cheng HH, Muir WM, Edelmann RE, Delany ME, Brugmann SA. The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant, talpid2. Development. 2014 Aug;141(15):3003-12.

Rada-Iglesias A, Bajpai R, Prescott S, Brugmann SA, Swigut T, Wysocka J. Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest. Cell Stem Cell. 2012 Nov 2;11(5):633-48.

Lenton K, James AW, Manu A, Brugmann SA, Birker D, Nelson ER, Leucht P, Helms JA, Longaker MT. Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis. 2011 Oct;49(10):784-96.

Powder KE, Ku YC, Brugmann SA, Veile RA, Renaud NA, Helms JA, Lovett M. A cross-species analysis of microRNAs in the developing avian face. PLoS One. 2012;7(4):e35111.

Kenneth J. Campbell, PhD

studies the molecular genetic control of mouse forebrain development with a particular focus on the generation of neuronal diversity in the ventral telencephalon.

513-636-0246 kenneth.campbell@cchmc.org

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Kenneth J. Campbell, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-0246

Fax 513-636-4317

Email kenneth.campbell@cchmc.org

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Molecular genetic control of mammalian forebrain development

MS: University of Toronto, Toronto, Canada, 1990.

PhD: University of Lund, Lund, Sweden, 1994.

Postdoctoral Fellow: Skirball Institute, NYU Med Center, 1995-97.

Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K. Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron. 2009;63:451-65.

Wang B, Waclaw RR, Allen ZJ II, Guillemot F, Campbell K. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon. Neural Development. 2009;4:5.

Waclaw RR, Allen Z, Bell SM, Erdelyi F, Szabo G, Potter SS, Campbell K. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron. 2006;49:503-16.

Campbell K. Cortical neuron specification: it has its time and place. Neuron. 2005;46:373-6.

Waclaw RR, Wang B, Campbell K. The homeobox gene Gsh2 is required for retinoid production in the embryonic mouse telencephalon. Development. 2004;131:4013-20.

Stenman J, Yu RT, Evans RM, Campbell K. Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the mouse telencephalon. Development. 2003;130:1113-22.

Stenman J, Toresson H, Campbell K. Identification of two distinct progenitor populations in the lateral ganglionic eminence: Implications for striatal and olfactory bulb neurogenesis. Journal of Neuroscience. 2003;23:167-74.

Sang-Wook Cha, PhD

investigates how Wnt/Planar Cell Polarity (PCP) signaling between lateral plate mesoderm (LPM) and endoderm regulates apicobasal polarity (ABP) of intestinal epithelium and controls radial-intercalation and gut elongation. Dr. Cha uses both amphibian and mouse/human organoids as the model systems.

513-803-3014 sang-wook.cha@cchmc.org

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Sang-Wook Cha, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3014

Email sang-wook.cha@cchmc.org

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Molecular basis of fetal intestine development; Wnt signaling; stem cells

PhD: College of Medicine, Kyungpook National University, South Korea, 2005.

Senior Researcher: Brain Korea21 project, 2005-2007.

Research Fellow/Associate: Cincinnati Children’s Research Foundation, Cincinnati, OH, 2007-2012.

View PubMed Publications.

Cha SW, McAdams M, Kormish J, Wylie C, Kofron M. Foxi2 is an animally localized maternal mRNA in Xenopus, and an activator of the zygotic ectoderm activator Foxi1e. PLoS ONE. 2012;7(7):e41782.

Nandadasa S, Tao Q, Shoemaker A, Cha SW, Wylie C. Regulation of classical cadherin membrane expression and F-actin assembly by alpha-catenins, during Xenopus embryogenesis. PLoS ONE. 2012;7(6):e38756.

Cha SW, Tadjuidje E, Wylie C, Heasman J. The roles of maternal Vangl2 and aPKC in Xenopus oocyte and embryo patterning. Development. 2011 Sep;138(18):3989-4000.

Tadjuidje E, Cha SW, Louza M, Wylie C, Heasman J. The functions of maternal Dishevelled 2 and 3 in the Early Xenopus embryo. Dev Dyn. 2011 Jul;240(7):1727-36.

Blythe SA, Cha SW, Tadjuidje E, Heasman J, Klein PS. beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2. Dev Cell. 2010 Aug 17;19(2):220-31.

Cha SW, Heasman J. Using oocytes for Wnt signaling assays: paracrine assays and Wnt-conditioned medium: review. Methods. 2010 May;51(1):52-5.

Cha SW, Tadjuidje E, White J, Wells J, Mayhew C, Wylie C, Heasman J. Wnt11/5a complex formation caused by tyrosine sulfation increases canonical signaling activity. Curr Biol. 2009 Sep 29;19(18):1573-80.

Vaughn G. Cleghon, PhD

is interested in understanding the role of protein kinases in development and disease. His lab uses molecular biology, tissue culture, Drosophila genetics and bioinformatics to better understand fundamental mechanisms involved in the regulation of protein kinase activity.
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513-803-0470 vaughn.cleghon@cchmc.org

Vaughn G. Cleghon, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-0470

Fax 513-636-4317

Email vaughn.cleghon@cchmc.org

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Protein kinases in development and human disease

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PhD: Waksman Institute of Microbiology, Rutgers, Piscataway, NJ, 1991.

Postdoctoral Fellow: Dr. Deborah Morrison ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research Center, Frederick, MD.

Group Leader: Beatson Institute for Cancer Research, Beatson Laboratories, UK.

Kinstrie R, Luebbering N, Miranda-Saavedra D, Sibbet G, Han J, Lochhead PA, Cleghon V. Characterization of a domain that transiently converts class 2 DYRKs into intramolecular tyrosine kinases. Sci Signal. 2010 Mar 2;3(111):ra16.

Day JP, Cleghon V, Houslay MD, Davies SA. Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein. Biochem J. 2008 Sep 15;414(3):363-74.

Lochhead PA, Kinstrie R, Sibbet G, Rawjee T, Morrice N, Cleghon V. A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop autophosphorylation. Mol Cell. 2006 Nov 17;24(4):627-33.

Kinstrie R, Lochhead PA, Sibbet G, Morrice N, Cleghon V. dDYRK2 and Minibrain interact with the chromatin remodeling factors SNR1 and TRX. Biochem J. 2006;398:45-54.

Lochhead PA, Sibbet G, Morrice N, Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell. 2005;121:925-36.

Roger Cornwall, MD Clinical Director, Pediatric Orthopaedic Surgery

investigates the neurological control of postnatal muscle growth and development. The goal of his research is to identify novel physiological treatments for pediatric neuromuscular contractures.

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513-636-4785

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Roger Cornwall, MD

Clinical Director, Pediatric Orthopaedic Surgery

Surgical Director, Epidermolysis Bullosa Center

Director, Hand and Upper Extremity Surgery Fellowship

Academic Affiliations

Associate Professor, UC Department of Orthopedic Surgery

Phone 513-636-4785

Fax 513-636-3928

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Clinical

Brachial plexus birth palsy; pediatric hand and wrist trauma; congenital hand and upper extremity abnormalities; complex pediatric elbow trauma and deformities; gymnast wrist.

Research

Brachial plexus injury and the growth and development of muscles; minimally invasive surgical treatment for shoulder contracture in brachial plexus birth palsy; nerve transfers for unreconstructable brachial plexus birth injuries; outcomes following surgical and nonsurgical treatment algorithms for pediatric hand fractures; outcomes of non-operative and operative treatment algorithms for chronic adolescent wrist pain.

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Biography

Dr. Cornwall is a full time pediatric hand and upper extremity surgeon who founded the Hand and Upper Extremity Center at Cincinnati Children's Hospital Medical Center in 2009. He is nationally known for his expertise in treating conditions that affect the pediatric hand and upper extremities, including complex trauma and congenital deformities, and brachial plexus injuries. He also runs a basic science laboratory investigating the neurological control of postnatal muscle growth, aiming to develop novel physiological treatments for neuromuscular contractures.

MD: Columbia University, New York, NY, 1997.

Residency: Orthopaedic Surgery, Mount Sinai Hospital, New York, NY, 2002.

Fellowship: Hand and Upper Extremity Surgery, Harvard University, Brigham and Women's Hospital, Massachusetts General Hospital, Children's Hospital Boston, Boston, MA, 2003.

Fellowship: Pediatric Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, 2004.

Visiting Fellowship: Pediatric Orthopaedic and Hand Surgery, Groote Schuur Hospital and Red Cross Children's Hospital, Cape Town, South Africa, 2004.

Visiting Fellowship: Pediatric Hand and Brachial Plexus Surgery, l'Institut de la Main, Paris, France, 2004.

Certification: American Board of Orthopaedic Surgery, 2006; Certificate of Added Qualifications in Surgery of the Hand, The American Board of Surgery, 2009.

Cheng W, Cornwall R, Crouch DL, Li Z, Saul KR. Contributions of Muscle Imbalance and Impaired Growth to Postural and Osseous Shoulder Deformity Following Brachial Plexus Birth Palsy: A Computational Simulation Analysis. J Hand Surg Am. 2015 Apr 3.

Eismann EA, Little KJ, Laor T, Cornwall R. Glenohumeral abduction contracture in children with unresolved neonatal brachial plexus palsy. J Bone Joint Surg Am. 2015 Jan 21;97(2):112-8.

Eismann EA, Lucky AW, Cornwall R. Hand function and quality of life in children with epidermolysis bullosa. Pediatr Dermatol. 2014 Mar-Apr;31(2):176-82.

Nikolaou S, Hu L, Tuttle LJ, Weekley H, Christopher W, Lieber RL, Cornwall R. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis. Muscle Nerve. 2014 Mar;49(3):398-404.

Eismann EA, Bauer A, Kozin SH, Louden E, Cornwall R. The relationship between medical malpractice litigation and parent reports of patient function following neonatal brachial plexus palsy. J Bone Joint Surg Am. 2014 Mar 5;96(5):373-9.

Eismann EA, Little KJ, Kunkel ST, Cornwall R. Clinical research fails to support more aggressive management of pediatric upper extremity fractures. J Bone Joint Surg Am. 2013 Aug 7;95(15):1345-50.

Reading BD, Laor T, Salisbury SR, Lippert WC, Cornwall R. Quantification of humeral head deformity following neonatal brachial plexus palsy. J Bone Joint Surg Am. 2012 Sep 19;94(18):e136(1-8).

Weekley H, Nikolaou S, Hu L, Eismann E, Wylie C, Cornwall R. The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury. J Orthop Res. 2012 Aug;30(8):1335-42.

Kunkel S, Eismann E, Cornwall R. Utility of the pediatric outcomes data collection instrument for assessing acute hand and wrist injuries in children. J Pediatr Orthop. 2011 Oct-Nov;31(7):767-72.

Nikolaou S, Peterson E, Kim A, Wylie C, Cornwall R. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury. J Bone Joint Surg Am. 2011 Mar 2;93(5):461-70.

Grants

The Role of Satellite Cells in Contracture Formation Following Neonatal Brachial Plexus Injury. Principal Investigator. Career Development Award, Orthopaedic Research and Education Foundation. Jul 2013-Jun 2016.

Steven A. Crone, PhD

focuses his research around understanding how neurons form functioning motor circuits during development and how the function (or dysfunction) of motor circuits impacts neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.
Visit the Crone Lab.

513-803-9275 steven.crone@cchmc.org

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Steven A. Crone, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-9275

Email steven.crone@cchmc.org

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Developmental biology; neurodegenerative disease; neural control of behavior; locomotion; respiration; motor circuits; amyotrophic lateral sclerosis (ALS); spinal muscular atrophy (SMA)

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Biography

Steven Crone, PhD, is an assistant professor in the Division of Pediatric Neurosurgery within the UC Department of Surgery. He received his BS with honors from The Pennsylvania State University in 1995. He received his PhD from the University of California, San Diego while performing his thesis research at The Salk Institute for Biological Studies.

His thesis research demonstrated that the ErbB2 receptor tyrosine kinase is essential for maintenance of the enteric nervous system and prevention of dilated cardiomyopathy. His research has important implications for the treatment of Hirschsprung’s disease, heart disease and ErbB2/Her2 dependent breast cancer.

Dr. Crone performed his postdoctoral work at the University of Chicago where he used transgenic mouse models to label, ablate or alter gene expression in specific interneurons to establish that V2a neurons coordinate limb movement during locomotion and promote a normal breathing rhythm.

He joined Cincinnati Children’s Hospital Medical Center in September of 2012 where his laboratory will investigate how motor circuits are altered by injury or disease.

BS: The Pennsylvania State University, University Park, PA, 1995.

PhD: University of California, San Diego and The Salk Institute for Biological Studies, San Diego, CA, 2003.

Postdoctoral: University of Chicago, Chicago, IL, 2012.

Crone SA, Viemari J-C, Droho S, Ramirez J, Mrejeru A, Sharma K. Irregular breathing in mice following genetic ablation of V2a neurons. J Neuroscience. 2012;32(23):7895–7906.

Zhong G, Droho S, Crone SA, Dietz S, Kwan AC, Webb WW, Sharma K, Harris-Warrick R. Electrophysiological characterization of the V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J Neuroscience. 2010;30(1):170-182.

Crone SA, Zhong G, Harris-Warrick R, Sharma K. In mice lacking V2a interneurons, gait depends on speed of locomotion. J Neuroscience. 2009;29(21):7098-7109.

Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE, Lundfald L, Endo T, Setlak J, Jessell TM, Kiehn O, Sharma K. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron. 2008;60:70-83.

Joseph NM, Mukouyama Y, Mosher JT, Jaegle M, Crone SA, Dormand E, Lee K-F, Meijer D, Anderson DJ, Morrison SJ. Neural crest stem cells undergo multi-lineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004;131:5599-5612.

Crone SA, Negro A, Trumpp A, Giovannini M, Lee K-F. Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system. Neuron. 2003;37:29-40.

Crone SA, Zhao Y-Y, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J Jr, Chien KR, Lee K-F. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nature Medicine. 2002;8:459-465.

Crone SA, Lee K-F. Gene targeting reveals multiple essential functions of the neuregulin signaling system during development of the neuroendocrine and nervous systems. Annals of the New York Academy of Sciences. 2002;971:547-553.

Kaspar BK, Vissel B, Bengoechea T, Crone S, Randolph-Moore L, Muller R, Brandon EP, Schaffer D, Verma IM, Lee K-F, Heinemann SF, Gage FH. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proceedings of the National Academy of Sciences USA. 2002;99:2320-5.

Tony J. De Falco, PhD

has basic research programs in gonad differentiation and homeostasis. His lab investigates how the initially undifferentiated gonad primordium transforms into a testis or ovary, as well as how the adult testis maintains sperm production over a long reproductive lifespan. His specific interests are in the novel and diverse roles of myeloid immune cells in reproductive biology.

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513-803-3988 tony.defalco@cchmc.org

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Tony J. De Falco, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3988

Email tony.defalco@cchmc.org

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Differentiation of the fetal gonad into a sexually dimorphic and structurally specialized organ; spermatogonial differentiation; roles of myeloid cells in tissue remodeling, organ vascularization and spermatogonial development.

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BA: University of Virginia, Charlottesville, VA.

PhD: Johns Hopkins University, Baltimore, MD.

Postdoc: Duke University Medical Center, Durham, NC.

Postdoc: National Institute of Genetics, Mishima, Japan.

DeFalco T*, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis**. Cell Rep. 2015;12(7):1107-19. (*corresponding author) (**Featured Article on the cover of the August 18th issue of Cell Reports, and also highlighted as a Preview in Cell Reports and as a featured article in the “World of Reproductive Biology” in Biology of Reproduction)

Potter SJ, DeFalco T. Using ex vivo upright droplet cultures of whole fetal organs to study developmental processes during mouse organogenesis. J Vis Exp. 2015;104:e53262.

DeFalco T*, Bhattacharya I, Williams AV, Sams, DM, Capel, B.* Yolk-sac-derived macrophages regulate fetal testis vascularization and morphogenesis. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):E2384-2393. (*co-corresponding authors)

DeFalco T, Saraswathula A, Briot A, Iruela-Arispe ML, Capel B. Testosterone levels influence mouse fetal Leydig cell progenitors through Notch signaling. Biol Reprod. 2013 Apr 11;884:91.

Jameson S, Natarajan A, Cool J, DeFalco T, Maatouk D, Mork L, Munger SC, Capel B. Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad. PLoS Genet. 2012;8(3):e1002575.

DeFalco T, Takahashi S, Capel B. Two distinct origins for Leydig cell progenitors in the fetal testis. Dev Biol. 2011 Apr 1;352(1):14-26.

Cool J, DeFalco TJ, Capel B. Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):167-172.

DeFalco T, Capel B. Gonad morphogenesis in vertebrates: divergent means to a convergent end. Annu Rev Cell Dev Biol. 2009;25:457-82.

DeFalco T, Camara N, Le Bras S, Van Doren M. Nonautonomous sex determination controls sexually dimorphic development of the Drosophila gonad. Dev Cell. 2008 Feb;14(2):275-86.

DeFalco TJ, Verney G, Jenkins AB, McCaffery JM, Russell S, Van Doren M. Sex-specific apoptosis regulates sexual dimorphism in the Drosophila embryonic gonad. Dev Cell. 2003 Aug;5(2):205-16.

Prasad Devarajan, MD Director, Division of Nephrology and Hypertension

researches acute kidney injury mechanisms, biomarkers and novel therapies. He also studies focal segmental glomerulosclerosis pathogenesis and biomarkers; and lupus nephritis molecular pathways and biomarkers. For each condition, his team employs an integrated approach of genomic and proteomic discovery in animal and human models, followed by translation, and validation in the human disease states.
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513-636-4531 prasad.devarajan@cchmc.org

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Prasad Devarajan, MD

Director, Division of Nephrology and Hypertension

Medical Director, Stone Center

Director, Nephrology and Hypertension Clinical Laboratory

Louise M. Williams Endowed Chair

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4531

Fax 513-636-7407

Email prasad.devarajan@cchmc.org

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Clinical specialties: acute kidney injury, nephrotic syndrome, kidney stones

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Premedical Studies: Bombay University, India, 1979.

MD: Bombay University, India, 1985.

Czech KA, Bennett M, Devarajan P. Distinct metalloproteinase excretion patterns in focal segmental glomerulosclerosis. Pediatr Nephrol. 2011 Jul 1.

Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, Ambalavanan N. Baseline Values of Candidate Urine Acute Kidney Injury (AKI) Biomarkers Vary by Gestational Age in Premature Infants. Pediatr Res. 2011 Jun 3.

Abraham BP, Frazier EA, Morrow WR, Blaszak RT, Devarajan P, Mitsnefes M, Bryant JC, Sachdeva R. Cystatin C and neutrophil gelatinase-associated lipocalin as markers of renal function in pediatric heart transplant recipients. Pediatr Transplant. 2011 Apr 25.

Sundaram N, Bennett M, Wilhelm J, Kim MO, Atweh G, Devarajan P, Malik P. Biomarkers for early detection of sickle nephropathy. Am J Hematol. 2011 Jul;86(7):559-66.

Devarajan P, Krawczeski C. In reply to 'antifibrinolytic use during cardiac and hepatic surgery makes tubular proteinuria-based early biomarkers poor tools to diagnose perioperative acute kidney injury'. Am J Kidney Dis. 2011 Jun;57(6):960-1.

Piyaphanee N, Ma Q, Kremen O, Czech K, Greis K, Mitsnefes M, Devarajan P, Bennett MR. Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome. Proteomics Clin Appl. 2011 Jun;5(5-6):334-42.

Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, Kim RW, Parikh CR; for the TRIBE-AKI Consortium. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: A prospective multicenter study. Crit Care Med. 2011 Jun;39(6):1493-1499.

Krawczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P. Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr. 2011 Jun;158(6):1009-1015.e1.

Basu RK, Devarajan P, Wong H, Wheeler DS. An update and review of acute kidney injury in pediatrics. Pediatr Crit Care Med. 2011 May;12(3):339-47.

Devarajan P. Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr. 2011 Apr;23(2):194-200.

Sudhansu K. Dey, PhD Lova Riekert Chair, Cancer and Cell Biology

investigates the paracrine, autocrine and juxtacrine signaling networks that influence uterine biology in the context of embryo-uterine interactions during pregnancy. He also works on the effects of endocannabinoids on periimplantation events. Studies involving the molecular and genetic regulation of epithelial ovarian cancer and uterine carcinoma are also of interest.
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513-803-1158 sk.dey@cchmc.org

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Sudhansu K. Dey, PhD

Lova Riekert Chair, Cancer and Cell Biology

Director, Division of Reproductive Sciences

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-1158

Fax 513-803-1160

Email sk.dey@cchmc.org

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Prostaglandin-nuclear receptor-angiogenic signaling axis during embryo implantation with special emphasis to cPLA2α-Cox2-PPARδ-Vegf network in the uterus; cytokine-growth factor-homeobox-morphogen signaling axis in implantation involving Lif-Hb-Egf-Hoxa10/Msx1-Ihh/Bmp/Wnt network in the uterus; immunophilin/cochaperone-nuclear signaling in the mouse uterus during implantation involving Fkbp52-PR; ligand-receptor signaling with endocannabinoids during the periimplantation events in mice in the context of anandamide interacting with G-protein coupled receptors, CB1 and CB2; molecular and genetic basis of epithelial ovarian cancer with special reference to prostaglandin-PPAR signaling; miRNA and Cox-2 regulation in uterine biology and cancer; Pten and uterine carcinoma: conditionally gene deleted mouse models

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Biography

Dr. Dey received his PhD from The University of Calcutta College of Sciences in 1972, after which he received postdoctoral training at the University of Kansas Medical Center from 1973-1977, followed by his faculty appointment in 1977 where he rose to the rank of University Distinguished Professor. He moved to Vanderbilt University as Dorothy Overall Wells professor of pediatrics, cell and developmental biology and pharmacology in 2002. In both places he directed NIH-funded reproductive biology training grants. In 2008, Dr. Dey moved to Cincinnati Children’s Hospital Medical Center as Lova Riekert Chair and professor of pediatrics within the University of Cincinnati College of Medicine to start a new Division of Reproductive Sciences. He has published over 300 original articles and has been funded by two MERIT Awards, RO1 grants and a Program Project Grants from NIH, and grants from the Bill and Melinda Gates Foundation and March of Dimes Foundation. His research mission has been to define the molecular road map to embryo-uterine interactions during pregnancy. His recent work published in Developmental Cell, Nat Med, PNAS and JCI provides novel information in the context of cell polarity in implantation, ectopic pregnancy, progesterone resistance to pregnancy failure and premature decidual senescence in preterm delivery. In 2008, Dr. Dey received Carl G. Hartman Award, the highest honor of the Society for the Study of Reproduction. In 2009, he received IVI Award sponsored by Schering-Plough for best contribution in reproductive medicine.

He has graduated seven PhD students and mentored over 40 postdoctoral fellows, 20 of whom are currently independent faculty members, and most others are investigators in major research institutions. His laboratory currently consists of one junior faculty, four postdoctoral fellows, one MD/PhD student, and two research assistants.

BSc: Presidency College, Calcutta, India, 1965.

MSc: University of Calcutta, India, 1967.

PhD: University of Calcutta, India, 1972.

Cha J, Bartos A, Egashira M, Haraguchi H, Saito-Fujita T, Leishman E, Bradshaw H, Dey SK, and Hirota Y. Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions. J Clin Invest. 2013 Sep 3;123(9):4063-75.

Raines AM, Adam M, Magella B, Meyer SE, Grimes HL, Dey SK, Potter SS. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development. 2013 Jul;140(14):2942-52.

Cha J, Sun X, Bartos A, Fenelon J, Lefevre P, Daikoku T, Shaw G, Maxson R, Murphy BD, Renfree MB, Dey SK. A new role for muscle segment homeobox genes in mammalian embryonic diapause. Open Biol. 2013 Apr 24;3(4):130035.

Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012 Dec:18(12):1754-67.

Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK. Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem. 2012 Sep 14;287(38):32288-97.

Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, Hirota Y, Lydon J, DeMayo F, Maxson R, Dey SK. Conditional Deletion of MSX Homeobox Genes in the Uterus Inhibits Blastocyst Implantation by Altering Uterine Receptivity. Dev Cell. 2011 Dec 13;21(6):1014-25.

Sun X, Xie H, Yang J, Wang H, Bradshaw HB, Dey SK. Endocannabinoid signaling directs differentiation of trophoblast cell lineages and placentation. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16887-92.

Hirota Y, Acar N, Tranguch S, Burnum KE, Xie H, Kodama A, Osuga Y, Ustunel I, Friedman DB, Caprioli RM, Daikoku T, Dey SK. Uterine FK506-binding protein 52 (FKBP52)-peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15577-82.

Hirota Y, Daikoku T, Tranguch S, Xie H, Bradshaw HB, Dey SK. Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. J Clin Invest. 2010 Mar;120(3):803-15.

Burnum KE, Cornett DS, Puolitaival SM, Milne SB, Myers DS, Tranguch S, Brown HA, Dey SK, RM Caprioli. Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation. J Lipid Res. 2009 Nov;50(11);2290-8.

Brian Gebelein, PhD

studies how the Hox genes specify distinct cell fates within the nervous system using the fruit fly as a model organism. His long-term goal is to use a combination of genetic and biochemical approaches to understand how Hox factors interact with neuronal transcription factors to regulate downstream target genes that pattern the nervous system and ultimately control cellular function and behavior.
Visit the Gebelein Lab.

513-636-3366 brian.gebelein@cchmc.org

Brian Gebelein, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-3366

Email brian.gebelein@cchmc.org

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Visit the Gebelein Lab.

BS: University of Wisconsin, Milwaukee, WI, 1994.

PhD: Mayo Graduate School, Rochester, MN, 2000.

Postdoctoral Fellow: Molecular mechanisms of Hox specificity in Drosophila melanogaster, Columbia University.

Charlton-Perkins M, Whitaker SL, Fei Y, Xie B, Li-Kroeger D, Gebelein B, Cook T. Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling. Neural Dev. 2011 May 3;6:20.

Gutzwiller LM, Witt LM, Gresser AL, Burns KA, Cook TA, Gebelein B. Proneural and abdominal Hox inputs synergize to promote sensory organ formation in the Drosophila abdomen. Dev Biol. 2010 Dec 15;348(2):231-43.

McDonald EC, Xie B, Workman M, Charlton-Perkins M, Terrell DA, Reischl J, Wimmer EA, Gebelein BA, Cook TA. Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events. Dev Biol. 2010 Nov 1;347(1):122-32.

Phelan JD, Shroyer NF, Cook T, Gebelein B, Grimes HL. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Curr Opin Hematol. 2010 Jul;17(4):300-7.

Witt LM, Gutzwiller LM, Gresser AL, Li-Kroeger D, Cook TA, Gebelein B. Atonal, Senseless, and Abdominal-A regulate rhomboid enhancer activity in abdominal sensory organ precursors. Dev Biol. 2010 Aug 15;344(2):1060-70.

Uhl JD, Cook TA, Gebelein B. Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements. Dev Biol. 2010 Jul 1;343(1-2):154-66.

Horman SR, Velu CS, Chaubey A, Bourdeau T, Zhu J, Paul WE, Gebelein B, Grimes HL. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood. 2009 May 28;113(22):5466-75.

Gebelein B. The control of EGF signaling and cell fate in the Drosophila abdomen. Fly (Austin). 2008 Sep-Oct;2(5):257-8.

Li-Kroeger D, Witt LM, Grimes HL, Cook TA, Gebelein B. Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Dev Cell. 2008 Aug;15(2):298-308.

Xie B, Charlton-Perkins M, McDonald E, Gebelein B, Cook T. Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development. 2007 Dec;134(23):4243-53.

Rashmi S. Hegde, PhD

studies molecular mechanisms involved in embryonic organ development and how the aberrant functioning of these processes can lead to developmental disorders as well as adult disease states such as cancer. This knowledge is then utilized in the rational design of therapeutic strategies. We use a variety of experimental techniques including biochemistry, cell biology and structural biology.
Visit the Hedge Lab.

513-636-5947 rashmi.hegde@cchmc.org

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Rashmi S. Hegde, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-5947

Fax 513-636-6772

Email rashmi.hegde@cchmc.org

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Clinical

Pre-clinical validation of anti-angiogenic agents for use in the treatment of retinopathies, cancer and pulmonary disease.

Research

Molecular mechanisms involved in normal development and in disease states using in vitro (cellular and solution biochemistry and structural biology) and in vivo (mouse models) strategies; developing novel therapeutic strategies via structure-aided drug design coupled with in vitro validation and in vivo pre-clinical studies.

Visit the Hegde Lab.

Biography

Rashmi Hegde received her PhD in medicinal chemistry from the University of Pittsburgh in 1989. She received post-doctoral training in the Department of Molecular Biophysics and Biochemistry at Yale University, where she was a fellow of the National Cancer Center. She was appointed assistant professor of biochemistry at New York University School of Medicine and the Skirball Institute of Biomolecular Medicine in 1994. She is presently a full professor in the Division of Developmental Biology at Children's Hospital Research Foundation within the Department of Pediatrics at the University of Cincinnati College of Medicine.

PhD: University of Pittsburgh, Pittsburgh, PA, 1989.

Post-doctoral Fellowship: Yale University, 1989-1994.

Assistant Professor: New York University School of Medicine, Skirball Institute, 1994-2000.

Associate Professor: Cincinnati Children's Hospital Medical Center, 2001-2007.

Professor: Cincinnati Children's Hospital Medical Center, 2008-present.

Hufnagel RB, Arno G, Hein ND, Hersheson J, Prasad M, Anderson Y, Laura A, Krueger LA, Gregory LC, Stoetzel C, Jaworek TJ, Hull S, Li A, Plagnol V, Willen CM, Morgan TM, Prows CA, Hegde RS, Riazuddin S, Grabowski GA, Richardson RJ, Dieterich K, Huang T, Revesv T, Martinez-Barbera JP, Sisk RA, Jefferies C, Houlden H, Dattani MT, Fink JK, Dollfus H, Moore AT, Ahmed ZM. Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes. J Med Genet. 2015 Feb;52(2):85-94.

Simon EM,Richard EM, Wang X, Shahzad M, Huang VH, Qaiser TA, Potluri P, Mahl SE, Davila A, Nazli S, Hancock S, Yu M, Gargus J, Chang R, Al-Sheqaih N, Newman WG, Abdenur J, Starr A, Hegde RS, Dorn T, Busch A, Park E, Wu J, Schwenzer H, Flieri A, Florentz C, Sissler M, Khan SN, Guan MX, Friedman TB, Wu DK, Procaccio V, Riazuddin S, Wallace DC, Ahmed ZM, Huang T, Riazuddin S. Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. PLoS Genetics. 2015 Mar 25;11(3):e1005097.

Seco CZ, Giese AP, Shafique S, Schraders M, Oonk AM, Grossheim M, Oostrik J, Strom T, Hegde R, van Wijk E, Frolenkov GI, Azam M, Yntema HG, Free RH, Riazuddin S, Verheij JB, Admiraal RJ, Qamar R, Ahmed ZM, Kremer H. Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells. Eur J Hum Genet. 2015 Jul 15. (Epub ahead of print).

Broering TJ, Wang YL, Pandey RN, Hegde RS, Wang SC, Namekawa SH. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis. Biol Open. 2015 May 15;4(7):873-84.

Pandey RN, Wang TS, Tadjuidje E, McDonald MG, Rettie AE, Hegde RS. Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agents. PLoS One. 2013 Dec 18;8(12):e84582.

Rao S, Chun C, Fan J, Kofron M, Hegde RS, Ferrara N, Yang MB, Copenhagen D, Lang RA. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature. 2013 Feb 14;494(7436):243-6.

Tadjuidje E, Hegde RS. The Eyes Absent proteins in development and disease. Cell Mol Life Sci. 2013 Jun;70(11):1897-913.

Korfhagen TR, Kitzmiller J, Chen G, Hegde RS, Divanovic S, Karp CL, Whitsett JA. SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune signaling during airway mucous metaplasia. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16630-5.

Riazuddin S, Belyantseva IA, Giese A, Kwanghyuk L, Indzhykulian A, Nandamuri SP, Yousaf R, Sue Lee, Terrell D, Hegde RS, Morell RJ, Ali RA, Anwar S, Rachel RA, Andrade-Elizondo PB, Sirmaci A, Husnain T, Khan SN, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Swaroop A, Ahmad W, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal S, Friedman TB, Ahmed Z. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 2012 Nov;44(11):1265-71.

Tadjuidje E, Wang TS, Pandey RN, Sumanas S, Lang RA, Hegde RS. The EYA tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromarone. PLoS One. 2012;7(4):e34806.

Stacey S. Huppert, PhD

investigates the cellular contribution and molecular factors required for assembly of the three-dimensional hepatic architecture, during liver development, homeostasis and regeneration. Defining the critical elements involved in formation and repair processes of the liver are necessary not only to understand biology, but also to identify the cellular and molecular targets involved in congenital and chronic liver diseases.

Visit the Huppert Lab.

513-803-3871 stacey.huppert@cchmc.org

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Stacey S. Huppert, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-3871

Email stacey.huppert@cchmc.org

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Hepatic development and regeneration; three-dimensional hepatic architecture; Notch signaling; hepatobiliary disease

Visit the Huppert Lab.

BS: Genetic Biology,Purdue University, West Lafayette, IN, 1992.

PhD: Genetics, Indiana University, Bloomington, IN, 1998.

Postdoctoral Fellow: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2003.

Instructor: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2005.

Assistant Professor: Cell and Developmental Biology, Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 2012.

Chen TW, Broadus MR, Huppert SS, Lee E. Reconstitution Of β-catenin Degradation In Xenopus Egg Extract. J Vis Exp. 2014 Jun 17;(88).

Poling HM, Mohanty SK, Tiao GM, Huppert SS. A comprehensive analysis of aquaporin and secretory related gene expression in neonate and adult cholangiocytes. Gene Expr Patterns. 2014 Jun 12;15(2):96-103.

Walter TJ, Cast AE, Huppert KA, Huppert SS. Epithelial VEGF signaling is required in the mouse liver for proper sinusoid endothelial cell identity and hepatocyte zonation in vivo. Am J Physiol Gastrointest Liver Physiol. 2014 May 15;306(10):G849-62.

Walter TJ, Vanderpool C, Cast AE, Huppert SS. Intrahepatic bile duct regeneration in mice does not require Hnf6 or Notch signaling through Rbpj. Am J Pathol. 2014 May;184(5):1479-88.

Walter TJ, Sparks EE, Huppert SS. 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile duct system. J Vis Exp. 2012 Oct 25;(68):e4272.

Hang BI, Thorne CA, Robbins DJ, Huppert SS, Lee LA, Lee E. Screening for small molecule inhibitors of embryonic pathways: sometimes you gotta crack a few eggs. Bioorg Med Chem. 2012 Mar 15;20(6):1869-77.

Humphreys R, Zheng W, Prince LS, Qu X, Brown C, Loomes K, Huppert SS, Baldwin S, Goudy S. Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients. Hum Mol Genet. 2012 Mar 15;21(6):1374-83.

Vanderpool C, Sparks EE, Huppert KA, Gannon M, Means AL, Huppert SS. Genetic interactions between hepatocyte nuclear factor-6 and Notch signaling regulate mouse intrahepatic bile duct development in vivo. Hepatology. 2012 Jan;55(1):233-43.

Sparks EE, Perrien DS, Huppert KA, Peterson TE, Huppert SS. Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice. Dis Model Mech. 2011 May;4(3):359-67.

Sparks EE, Huppert KA, Brown MA, Washington MK, Huppert SS. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology. 2010 Apr;51(4):1391-400.

Rulang Jiang, PhD Member, Division of Developmental Biology

is a developmental biologist directing research programs in craniofacial biology. His lab generates and uses mutant mouse models to investigate the genetic and developmental basis of craniofacial birth defects, including cleft lip, cleft palate, tooth defects, and other craniofacial deformities. His lab also studies development of joints, including long bone joints in the limb and the temporomandibular joint of the jaw.

Visit the Jiang Lab.

513-636-3212 rulang.jiang@cchmc.org

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Rulang Jiang, PhD

Member, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3212

Email rulang.jiang@cchmc.org

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BS: Nanjing Normal University, Nanjing, China, 1984.

MS: Genetics, Chinese Academy of Sciences, Beijing, China, 1987.

PhD: Wesleyan University, Middletown, CT, 1995.

Gao Y, Lan Y, Liu H, Jiang R. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev Biol. 2011 Apr;352(1):83-91.

Baek JA, Lan Y, Liu H, Maltby KM, Mishina Y, Jiang R. Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation. Dev Biol. 2011 Feb;350(2):520-531.

Liu W, Watson SS, Lan Y, Keene DR, Ovitt CE, Liu H, Schweitzer R, Jiang R. The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis. Mol Cell Biol. 2010 Oct;30(20):4797-4807.

Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009 Apr;136(8):1387-1396.

Zhang Z, Lan Y, Chai Y, Jiang R. Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row. Science. 2009;323(5918):1232-1234.

Lan Y, Wang Q, Ovitt CE, Jiang R. A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development. Genesis. 2007;45(10):618-624.

Jiang R, Bush JO, Lidral AC. Development of the upper lip: morphogenetic and molecular mechanisms. Dev Dyn. 2006;235(5):1152-1166.

Wang Q, Lan Y, Cho ES, Maltby KM, Jiang R. Odd-skipped related 1 (Odd1) is an essential regulator of heart and urogenital development. Dev Biol. 2005;288(2):582-594.

Lan Y, Ovitt CE, Cho ES, Maltby KM, Wang Q, Jiang R. Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis. Development. 2004;131(13):3207-3216.

Bush JO, Lan Y, Jiang R. The cleft lip and palate defects in the Dancer mutant mice result from gain of function of the Tbx10 gene. Proc Nat Acad Sci U S A. 2004;101(18):7022-7027.

Vladimir V. Kalinichenko, MD, PhD

is investigating the transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis. He studies the winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival, ultimately identifying novel mechanisms that cause human lung malformations and promote lung cancer formation.

513-636-4822 vladimir.kalinichenko@cchmc.org

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Vladimir V. Kalinichenko, MD, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4822

Fax 513-636-2423

Email vladimir.kalinichenko@cchmc.org

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Clinical

Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.

Research

Transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis; winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival; identify and increase understanding of currently unknown mechanisms that cause human lung malformations and promote lung cancer formation.

MD: Russian State Medical University, Moscow, Russia, 1993.

PhD: Russian State Medical University, Moscow, Russia, 1995.

Fellowship: From the European Soros Foundation, 1995.

Postdoctoral: University of Illinois at Chicago, Center for Molecular Biology, IL, 2000.

Postdoctoral: University of Illinois at Chicago, Department of Molecular Genetics, IL, 2002.

Wang IC, Ustiyan V, Zhang Y, Cai Y, Kalin TV, Kalinichenko VV. Foxm1 transcription factor is required for the initiation of lung tumorigenesis by oncogenic KrasG12D. Oncogene. 2014 Nov13;33(46):5391-6.

Ren X, Shah T, Ustiyan V, Zhang Y, Shinn J, Chen G, Whitsett JA, Kalin TV, Kalinichenko VV. FOXM1 Promotes Allergen-Induced Goblet Cell Metaplasia and Pulmonary Inflammation. Mol Cell Biol. 2013 Jan;33(2):371-86.

Wang IC, Snyder J, Zhang Y, Lander J, Nakafuku Y, Lin J, Chen G, Kalin TV, Whitsett JA, Kalinichenko VV. Foxm1 mediates a cross-talk between Kras/MAPK and canonical Wnt signaling pathways during development of respiratory epithelium. Mol Cell Biol. 2012 Oct;32(19):3838-50.

Ustiyan V, Wert SE, Ikegami M, Wang IC, Kalin TV, Whitsett JA, Kalinichenko VV. Foxm1 Transcription Factor Is Critical for Proliferation and Differentiation of Clara Cells during Development of Conducting Airways. Dev Biol. 2012 Oct 15;370(2):198-212.

Ren X, Zhang Y, Snyder J, Cross ER, Shah TA, Kalin TV, Kalinichenko VV. Forkhead Box M1 Transcription Factor Is Required for Macrophage Recruitment during Liver Repair. Mol Cell Biol. 2010 Nov;30(22):5381-93.

Wang IC, Zhang Y, Snyder J, Sutherland MJ, Burhans MS, Shannon JM, Park HJ, Whitsett JA, . Kalinichenko VV. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia. Dev Biol. 2010 Nov 15;347(2):301-14.

Ustiyan V, Wang IC, Ren X, Zhang Y, Snyder J, Xu Y, Wert SE, Lessard JL, Kalin TV, Kalinichenko VV. Forkhead Box M1 Transcriptional Factor is Required for Smooth Muscle Cells during Embryonic Development of Blood Vessels and Esophagus. Dev Biol. 2009 Dec 15;336(2):266-79.

Kalin TV, Wang IC, Meliton L, Zhang Y, Wert SE, Ren X, Snyder J, Graf L Jr, Whitsett JA, Kalinichenko VV. Forkhead Box M1 Transcription Factor is Required for Perinatal Lung Function. Proc Natl Acad Sci USA. 2008 Dec;9105(49):19330-5.

Malin D, Kim IM, Boetticher E, Kalin TV, Ramakrishna S, Meliton L, Ustiyan V, Zhu X, Kalinichenko VV. Forkhead Box F1 Is Essential for Migration of Mesenchymal Cells and Directly Induces Integrin-Beta3 Expression. Mol Cell Biol. 2007 Apr;27(7):2486-98.

Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV. The Forkhead Box m1 Transcription Factor Stimulates the Proliferation of Tumor Cells during Development of Lung Cancer. Cancer Res. 2006 Feb 15;66(4):2153-61.

J. Matthew Kofron, PhD Research Associate, Division of Developmental Biology

513-636-4425 matthew.kofron@cchmc.org

Raphael Kopan, PhD Director, Division of Developmental Biology

and his lab have the long-term goal of organogenesis in vitro. They focus their efforts on Notch signaling as their lead into mechanistic understanding of tissue diversity using genetic engineering, embryology and single cell profiling. They interrogate the mouse embryo to address critical questions regarding the circuit logic of Notch signaling in mammalian organogenesis and its integration in larger signaling context.

Visit the Kopan Lab.

513-636-1299

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Raphael Kopan, PhD

Director, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1299

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Notch signaling; kidney organogenesis; skin organogenesis; TSLP signaling in cancer

Visit the Kopan Lab.

Biography

Raphael Kopan, PhD, who is a professor of developmental biology at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine, has carried out seminal work in the field of Notch biology. This work has, and continues to have, an enormous impact on our understanding of normal tissue development and renewal, Alzheimer's disease and cancer-related research. In deciphering the mode of Notch activation and demonstrating the use of inhibitors to modulate Notch activity, Dr. Kopan's work laid the groundwork for the therapeutic use of γ-secretase inhibitors in the treatment of cancers, currently in clinical trials. His current interests in organogenesis are focused on two modular organs - skin and kidney - in which his group is trying to understand how interplay among the same seven pathways results in activation of distant programs. Dr. Kopan's work has resulted in 120 scientific articles as of 2013. He is the co-inventor of one patent, and he has served on scientific advisory boards as well as being a consultant to the pharmaceutical industry.

BS, MsC: Department of Zoology, Tel-Aviv University, Israel.

PhD: Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL.

Post-doctoral training : The Fred Hutchinson Cancer Research Center, Seattle, WA.

Hass MR, Liow HH, Chen X, Sharma A, Inoue YU, Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R. SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. Molecular Cell. 2015;9(4):685-697.

Demitrack ES, Gifford GB, Keeley TM, Carulli AJ, VanDussen KL, Thomas D, Giordano TJ, Liu Z, Kopan R, Samuelson LC. Notch signaling regulates gastric antral LGR5 stem cell function. EMBO J. 2015 Aug 12.

Liu Z, Brunskill E, Varnum-Finney B, Zhang C, Zhang A, Jay PY, Bernstein I, Morimoto M, Kopan R. The intracellular domains of Notch1 and 2 are functionally equivalent during development and carcinogenesis. Development. 2015;142:2452-2463.

Liu Z, Brunskill E, Boyle S, Chen S, Turkoz M, Guo Y, Grant R, Kopan R. Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity. Development. 2015 Mar 15;142(6):1193-202.

Demehri S, Yockey LJ, Visness CM, Jaffee KF, Turkoz A, Wood RA, O'Connor GT, Kattan M, Gern JE, Gergen PJ, Holtzman M, Bloomberg G, Kopan R. Circulating TSLP associates with decreased wheezing in non-atopic preschool children: Data from the URECA birth cohort. Clin Exp Allergy. 2014 Jun;44(6):851-7.

Zhao ZQ, Huo FQ, Jeffry J, Hampton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF Jr, Zhong J, Chen ZF. Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest. 2013 Nov;123(11):4769-80.

Chillakuri CR, Sheppard D, Ilagan MX, Holt LR, Abbott F, Liang S, Kopan R, Handford PA, Lea SM. Structural analysis uncovers lipid-binding properties of notch ligands. Cell Rep. 2013 Nov 27;5(4):861-7.

Boyle SC1, Liu Z, Kopan R. Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development. 2014 Jan;141(2):346-54.

Satpathy AT, Briseño CG, Lee JS, Ng D, Manieri NA, Kc W, Wu X, Thomas SR, Lee WL, Turkoz M, McDonald KG, Meredith MM, Song C, Guidos CJ, Newberry RD, Ouyang W, Murphy TL, Stappenbeck TS, Gommerman JL, Nussenzweig MC, Colonna M, Kopan R, Murphy KM. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013 Sep;14(9):937-48.

Yu Lan, PhD Member, Division of Plastic Surgery

is interested in understanding the genetic basis and developmental mechanisms of structural birth defects. Specifically, Dr. Lan investigates the molecular pathways governing normal palate development in laboratory mice. Her ongoing investigations focus on delineating the molecular pathways involving these factors in palate development using a combination of genetic, embryological, and biochemical approaches.

Visit the Lan Lab.

513-803-7842 yu.lan@cchmc.org

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Yu Lan, PhD

Member, Division of Plastic Surgery

Academic Affiliations

Associate Professor, UC Department of Surgery

UC Department of Pediatrics

Phone 513-803-7842

Email yu.lan@cchmc.org

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Visit the Lan Lab.

Biography

Yu Lan, PhD, is interested in understanding the genetic basis and developmental mechanisms of structural birth defects. Specifically, Dr. Lan investigates the molecular pathways governing normal palate development in laboratory mice. Her ongoing investigations focus on delineating the molecular pathways involving these factors in palate development using a combination of genetic, embryological, and biochemical approaches.

PhD: University of Maine, Orono, ME.

Post-doc training: Wesleyan University, Middletown, CT; The Jackson Laboratory, Bar Harbor, ME.

Lan Y, Jia S, Jiang R. Molecular patterning of the mammalian dentition. Semin Cell Dev Biol. 2014 Jan-Feb;25-26: 61-70.

Liu H, Lan Y, Xu J, Chang CF, Brugmann SA, Jiang R. Odd-skipped related-1 controls neural crest chondrogenesis during tongue development. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18555-60.

Xu J, Liu H, Park JS, Lan Y, Jiang R. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis. Development. 2014 Apr;141(7):1442-52.

Zhou H, Zou S, Lan Y, Fei W, Jiang R, Hu J. Smad7 modulates TGFbeta signaling during cranial suture development to maintain suture patency. J Bone Miner Res. 2014 Mar;29(3):716-24.

Zhou J, Gao Y, Lan Y, Jia S, Jiang R. Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis. Development. 2013 Dec;140(23):4709-18.

Lan Y, Liu H, Ovitt CE, Jiang R. Generation of Osr1 conditional mutant mice. Genesis. 2011 May;49(5):419-22.

Gao Y, Lan Y, Liu H, Jiang R. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev Biol. 2011 Apr 1;352(1):83-91.

Baek JA, Lan Y, Liu H, Maltby KM, Mishina Y, Jiang R. Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation. Dev Biol. 2011 Feb 15;350(2):520-31.

Chen J, Lan Y, Baek JA, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009 Oct 1;334(1):174–85.

Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009 Apr;136(8):1387-96.

Richard A. Lang, PhD Director, Visual Systems Group

has two major research interests. First, the lab is interested in mechanisms of signaling and morphogenesis in early eye development. Second, they investigate the role macrophages play in regulating vascularity during development and homeostasis.
Visit the Lang Lab.

513-636-2700 richard.lang@cchmc.org

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Richard A. Lang, PhD

Director, Visual Systems Group

Academic Affiliations

Professor, UC Department of Pediatrics

UC Department of Ophthalmology

Phone 513-636-2700

Fax 513-803-0740

Email richard.lang@cchmc.org

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Wnt ligands in tumorigenesis; vascular regression and tissue regeneration; lens induction and morphogenesis.

Visit the Lang Lab.

BSc: Co-major in genetics and biochemistry, University of Melbourne, Australia, 1984 (with honors).

PhD: University of Melbourne, Australia, at the Ludwig Institute for Cancer Research under Drs. AR Dunn and TJ Gonda, 1988.

Postdoctoral Fellow: The G.W. Hooper Research Foundation, University of California, San Francisco under Dr. JM Bishop, 1989-92. Studied the role of the macrophage in developmentally programmed tissue remodeling.

Yeo EJ, Cassetta L, Qian BZ, Lewkowich I, Li JF, Stefater JA 3rd, Smith AN, Wiechmann LS, Wang Y, Pollard J, Lang RA. Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res. 2014 Jun 1;74(11):2962-73.

Rao S, Chun C, Fan J, Kofron JM, Yang MB, Hegde RS, Ferrara N, Copenhagen DR, Lang RA. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature. 2013;494(7436):243-6.

Stefater JA 3rd, Lewkowich I, Rao S, Mariggi G, Carpenter AC, Burr AR, Fan J, Ajima R, Molkentin JD, Williams BO, Wills-Karp M, Pollard JW, Yamaguchi T, Ferrara N, Gerhardt H, Lang RA. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature. 2011 May 29;474(7352):511-5.

Chauhan BK, Lou M, Zheng Y, Lang RA. Balanced Rac1 and RhoA activities regulate cell shape and drive invagination morphogenesis in epithelia. PNAS. 2011 Nov 8;108(45):18289-94.

Plageman TF Jr, Chung MI, Lou M, Smith AN, Hildebrand JD, Wallingford JB, Lang RA. Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development. 2010 Feb;137(3):405-15.

Lobov IB, Rao S, Carroll TJ, Vallance JE, Ito M, Ondr JK, Kurup S, Glass DA, Patel MS, Shu W, Morrisey EE, McMahon AP, Karsenty G, Lang RA. Wnt7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature. 2005 Sep 15;437(7057):417-21.

Xinhua Lin, PhD

is interested in cell-cell signaling mechanisms that control tissue patterning during development. His lab focuses on the role of heparan sulfate proteoglycans in morphogen distribution and signaling. The Lin Lab also studies the molecular mechanisms of Wnt signaling in development.

513-636-2144 xinhua.lin@cchmc.org

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Xinhua Lin, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-2144

Fax 513-636-4317

Email xinhua.lin@cchmc.org

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Understanding the mechanisms governing the regulation of cell-cell signaling by extracellular molecules that play essential roles in coordinating cell growth and differentiation; the role of heparan sulfate proteoglycans (HSPGs) in cell-cell signaling; identification of molecules that modulate the function of two key signaling molecules, Wnt/Wingless (Wg), Hedgehog (Hh).

Biography

Xinhua Lin, PhD, completed his doctoral work at the Washington University with Thomas. F. Deuel, where he studied the transcriptional regulation of platelet-derived growth factor A-chain gene. He then went to the Dr. Norbert Perrimon lab at Harvard Medical School, where he initiated his work on the role of heparan sulfate proteoglycan in cell-cell signaling in drosophila.

Dr. Lin has identified and characterized two mutations, sugarless and sulfateless, which occur in the genes that encode essential enzymes for the biosynthesis of heparin/heparin sulfate glycosaminoglycan (HSPG). Analyses of these mutants led to the demonstration that HSPGs play critical roles in the signaling activities of several growth factors including Wg, Hh and FGF. Dr. Lin further demonstrated that glypican members of HSPG play key roles in Wg signaling and the formation of Wg morphogen gradient. He became an assistant professor in April, 2000, at Cincinnati Children's Hospital Medical Center. His lab is interested in elucidating the molecular mechanisms of cell-cell signaling, focusing on the role of HSPG in signaling and the morphogen gradient formation of the Wg and Hh proteins.

BS: Hangchou University, Hangchou, P.R. China, 1984.

MS: Shanghai Institute of Cell Biology, Academia Sinica, P.R. China, 1987.

PhD: Washington University, St. Louis, MO, 1995.

Fellowship: Postdoctoral Research Fellow, Howard Hughes Medical Institute/Harvard Medical School, Cambridge, MA, 1995-2000.

You J, Belenkaya T, Lin X. Sulfated is a negative feedback regulator of wingless in Drosophila. Dev Dyn. 2011 Feb 8. doi: 10.1002/dvdy.22562.

Deng J, Deng L, Su S, Zhang M, Lin X, Wei L, Minai AA, Hassett DJ, Lu LJ. Investigating the predictability of essential genes across distantly related organisms using an integrative approach. Nucleic Acids Res. 2011 Feb 1;39(3):795-807.

Yan D, Wu Y, Yang Y, Belenkaya TY, Tang X, Lin X. The cell-surface proteins Dally-like and Ihog differentially regulate Hedgehog signaling strength and range during development. Development. 2010 Jun;137(12):2033-44.

Yan D, Lin X. Shaping morphogen gradients by proteoglycans. Cold Spring Harb Perspect Biol. 2009 Sep;1(3):a002493. Review.

Yan D, Wu Y, Feng Y, Lin SC, Lin X. The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. Dev Cell. 2009 Oct;17(4):470-81.

Lin X, Pittman J, Clarke B. Information Conversion, Effective Samples, and Parameter Size. IEEE Trans Inf Theory. 2007 Dec;53(12):4438-4456.

Chen Y, Guo JJ, Healy DP, Lin X, Patel NC. Risk of hepatotoxicity associated with the use of telithromycin: a signal detection using data mining algorithms. Ann Pharmacother. 2008 Dec;42(12):1791-6.

He F, Wen Y, Deng J, Lin X, Lu LJ, Jiao R, Ma J. Probing intrinsic properties of a robust morphogen gradient in Drosophila. Dev Cell. 2008 Oct;15(4):558-67.

Yan D, Lin X. Opposing roles for glypicans in Hedgehog signalling. Nat Cell Biol. 2008 Jul;10(7):761-3.

Belenkaya TY, Wu Y, Tang X, Zhou B, Cheng L, Sharma YV, Yan D, Selva EM, Lin X. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Dev Cell. 2008 Jan;14(1):120-31.

Jun Ma, PhD

researches developmental processes at a quantitative and systems level. His team investigates fundamental mechanisms of development through a combination of quantitative experimental approaches and theoretical and simulation approaches.

513-636-7977 jun.ma@cchmc.org

High Res

Jun Ma, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7977

Fax 513-636-4317

Email jun.ma@cchmc.org

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Molecular mechanisms of gene regulation and embryonic development

Biography

Research performed by Dr. Ma’s team focuses on understanding developmental processes at a quantitative and systems level. His team investigates fundamental mechanisms of development through a combination of quantitative experimental approaches and theoretical and simulation approaches. One major focus of Ma’s lab concerns the questions of how morphogen gradients are established, and how precise positional information is encoded by these gradients and interpreted by cells in developing tissues. In a recent study that the team reported in a Nature Communications paper (2015), they establish a mathematical model to quantitatively connect two different stages of the life cycle of the fruit fly Drosophila: oocyte formation and embryonic pattern specification. Their reported study provides a fresh view of how the resources are accumulated by the mother for the purpose of instructing robust development of the future embryo.

BS: Peking University, 1978-1982.

PhD: Harvard University, Cambridge, MA, 1983-1988 (degree awarded 1990).

Wu H, Manu Jiao R, Ma J. Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila. Nat Commun. 2015.

Liu J, Ma J. Modulation of temporal dynamics of gene transcription by activator potency in the Drosophila embryo. Development. 2015;142:3781-3790.

Cheung D, Ma J. Probing the impact of temperature on molecular events in a developmental system. Sci Rep. 2015;5:13124.

He F, Wei C, Wu H, Cheung D, Jiao R, Ma J. Fundamental origins and limits for scaling a maternal morphogen gradient. Nat Commun. 2015;6:6679.

Cheung D, Miles C, Kreitman M, Ma J. Adaptation of the length scale and amplitude of the Bicoid gradient profile to achieve robust patterning in abnormally large Drosophila melanogaster embryos. Development. 2014;141(1):124-135.

Liu J, Ma J. Dampened regulates the activating potency of Bicoid and the embryonic patterning outcome in Drosophila. Nat Commun. 2013;4:2968.

He F, Ren J, Wang W, Ma J. Evaluating the Drosophila Bicoid morphogen gradient system through dissecting the noise in transcriptional bursts. Bioinformatics. 2012;28:970-975.

Liu J, Ma J. Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos. Nat Cell Biol. 2011 Jan;13(1):22-9.

Cheung D, Miles C, Kreitman M, Ma J. Scaling of the Bicoid morphogen gradient by a volume-dependent production rate. Development. 2011;138:2741-2749.

He F, Wen Y, Deng J, Lin X, Lu LJ, Jiao R, Ma J. Probing intrinsic properties of a robust morphogen gradient in Drosophila. Dev Cell. 2008 Oct;15(4):558-67.

Christopher N. Mayhew, PhD Co-Director, Pluripotent Stem Cell Facility

is co-director of the Pluripotent Stem Cell Facility. His lab functions as a core facility providing access for Cincinnati Children's / University of Cincinnati investigators to highly quality controlled human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells. In addition, the lab provides training in the culture and manipulation of human pluripotent stem cells to investigators.

513-636-3744 christopher.mayhew@cchmc.org

Masato Nakafuku, MD, PhD Ohio Eminent Scholar

is focused on the development and regeneration of the mammalian central nervous system (CNS). He is seeking to understand the molecular mechanisms underlying normal development of the CNS and is also interested in applying advancement of knowledge on neural development for developing novel therapeutic strategies to cure neurological diseases.
Visit the Nakafuku Lab.

513-636-9389 masato.nakafuku@cchmc.org

Masato Nakafuku, MD, PhD

Ohio Eminent Scholar

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-9389

Fax 513-636-4317

Email masato.nakafuku@cchmc.org

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Development and regeneration of the central nervous system (CNS); therapeutic strategies for neurological diseases

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PhD: Graduate School of Medical Sciences, University of Tokyo, Tokyo, Japan, 1988.

MD: The University of Kanazawa School of Medicine, Japan, 1984.

Pei Z, Wang B, Chen G, Nagao M, Nakafuku M, Campbell K. Homeobox genes Gsx1 and Gsx2 differentially regulate telencephalic progenitor maturation. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1675-80.

Shereen A, Nemkul N, Yang D, Adhami F, Dunn RS, Hazen ML, Nakafuku M, Ning G, Lindquist DM, Kuan CY. Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke. J Cereb Blood Flow Metab. 2010 Dec 8.

Nagao M, Campbell K, Burns K, Kuan CY, Trumpp A, Nakafuku M. Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF-p53 pathway. J Cell Biol. 2008 Dec 29;183(7):1243-57.

Sugimori M, Nagao M, Parras CM, Nakatani H, Lebel M, Guillemot F, Nakafuku M. Ascl1 is required for oligodendrocyte development in the spinal cord. Development. 2008 Apr;135(7):1271-81.

Nakafuku M, Nagao M, Grande A, Cancelliere A. Revisiting neural stem cell identity. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):829-30.

Kim HJ, Sugimori M, Nakafuku M, Svendsen CN. Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1. Exp Neurol. 2007 203:394-405.

Nagao M, Sugimori M, Nakafuku M. Cross talk between notch and growth factor/cytokine signaling pathways in neural stem cells. Mol Cell Biol. 2007 Jun;27(11):3982-94.

Parras CM, Hunt C, Sugimori M, Nakafuku M, Rowitch D, Guillemot F. The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes. J Neurosci. 2007 27:4233-4242.

Sugimori M, Nagao M, Bertrand N, Parras CM, Guillemot F, Nakafuku M. Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development. 2007 Apr;134(8):1617-29.

Ohori Y, Yamamoto S, Nagao M, Sugimori M, Yamamoto N, Nakamura K, Nakafuku M. Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord. J Neurosci. 2006 Nov 15;26(46):11948-60.

Takahisa Nakamura, PhD

Research goal is to address questions concerning why and how inflammatory responses are initiated, coordinated, and thus involved in the development of obesity-induced metabolic diseases.

513-636-4744 takahisa.nakamura@cchmc.org

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Takahisa Nakamura, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-4744

Email takahisa.nakamura@cchmc.org

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RNA-related inflammation in obesity and metabolic diseases

Biography

Dr. Nakamura received his PhD from the University of Tokyo in 2003. He completed postdoctoral training in the laboratory of Dr. Gökhan S. Hotamisligil at Harvard School of Public Health in 2013, followed by his faculty appointment at Cincinnati Children's Hospital Medical Center within the UC Department of Pediatrics in 2013.

PhD: University of Tokyo, 2003.

Postdoctoral Fellow: University of Tokyo, 2003-2006.

Research Fellow: Harvard University, 2006-2010.

Research Associate: Harvard University, 2010-2013.

Nakamura T, Arduini A, Baccaro B, Furuhashi M, Hotamisligil GS. Small molecule inhibitors of PKR improve glucose homeostasis in obese, diabetic mice. Diabetes. 2014 Feb;63(2):526-34.

Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012 Aug 20;488(7413):670-4.

Morita M. Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T. Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3(+/-) mice. EMBO J. 2011 Sep 6;30(22):4678-4691.

Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS. Double-stranded RNA-dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell. 2010 Feb 5;140(3):338-48.

Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y, Kakuta S, Sudo K, Iwakura Y, Shibutani M, Mitsumori K, Yokota J, Yamamoto T. Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma. Cancer Sci. 2009 Feb;100(2):224-232.

Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T. Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. FEBS Lett. 2008 Apr 16;582(9):1313-8.

Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007 Jul;27(13):4980-90.

Nakamura T, Yao R, Ogawa T, Suzuki T, Ito C, Tsunekawa N, Inoue K, Ajima R, Miyasaka T, Yoshida Y, Ogura A, Toshimori K, Noce T, Yamamoto T, Noda T. Oligoasthenoteratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet. 2004 May;36(5):528-33.

Kimura H*, Nakamura T*, Ogawa T, Tanaka S, Shiota K. Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. Nucleic Acids Res. 2003 Jun 15;31(12):3101-13. *These authors contributed equally to this work.

Yoshida Y*, Nakamura T*, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003 May 15;17(10):1201-6. *These authors contributed equally to this work.

Grants

Analysis of pathogenic double-stranded RNA in chronic inflammatory diseases. Principal Investigator. Japan Science and Technology Agency, PRESTO. Feb 2013–Mar 2016.

Satoshi H. Namekawa, PhD

examines the mechanisms and evolution of epigenetic events during mammalian reproduction, using a male germ cell model.
Visit the Namekawa Lab.

513-803-1377 satoshi.namekawa@cchmc.org

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Satoshi H. Namekawa, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-1377

Fax 513-803-1160

Email satoshi.namekawa@cchmc.org

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The long-term goal of Dr. Namekawa's research is to understand the mechanisms and evolution of epigenetic events during mammalian reproduction. One of the focus areas is epigenetic regulation of sex chromosomes in germ cell development. Recently, his laboratory demonstrated that DNA damage response pathways trigger epigenetic programming on the sex chromosomes in germ cells. An on-going direction of the laboratory is to pursue a general link between DNA damage response pathways and epigenetic programming. Another goal of the laboratory is to identify novel factors and related pathways that control epigenetic programming during mouse reproduction, especially focusing on the events occurring on sex chromosomes during spermatogenesis as well as the regulatory mechanisms in germline stem cells.

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Biography

Dr. Namekawa received his PhD from Tokyo University of Science in 2005. He completed postdoctoral training in the laboratory of Dr. Jeannie T. Lee at Massachusetts General Hospital and Harvard Medical School in 2009, followed by his faculty appointment at Cincinnati Children's in 2009. He is funded by NIH R01 Award and the Basil O’Connor Award from March of Dimes Foundation.

He received the 2015 New Investigator Award from the Society for the Study of Reproduction.

PhD: Tokyo University of Science, Japan, 2005.

BS: Tokyo University of Science, Japan, 2000.

Sin HS, Kartashov AV, Hasegawa K,Barski A, Namekawa SH. Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline. BMC Biol. 2015 Jul 22;13:53.

Kato Y, Alavattam KG, Sin HS, Meetei A, Pang Q, Andreassen PR, Namekawa SH. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015 Jun 29.

Broering TJ, Wang YL, Pandey RN, Hegde RS, Wang SC, Namekawa SH. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis. Biol Open. 2015 May 15.

Hu YC, Namekawa SH. Functional significance of the sex chromosomes during spermatogenesis. Reproduction. 2015 Jun;149(6):R265-R277.

Hasegawa K, Sin HS, Maezawa S, Broering TJ, Kartashov AV, Alavattam KG, Ichijima Y, Zhang F, Bacon WC, Greis KD, Andreassen PR, Barski A, Namekawa SH. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 2015 Mar 9;32(5):574-88.

Broering TJ*, Alavattam KG*, Sadreyev RI, Ichijima Y, Kato Y, Hasegawa K, Camerini-Otero RD, Lee JT, Andreassen PR, Namekawa SH. BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis. (*equal contribution) J Cell Biol. 2014 Jun 9;205(5):663-75.

Namekawa SH. Slide preparation method to preserve three-dimensional chromatin architecture of testicular germ cells.J Vis Exp. 2014 Jan 10;(83).

Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in postmeiotic spermatids. Genes Dev. 2012 Dec 15:26(24)2737-2748.

Sin HS, Ichijima Y, Koh E, Namiki M, Namekawa SH. Human post meiotic sex chromatin and its impact on sex chromosome evolution. Genome Res. 2012 May;22(5):827-36.

Ichijima, Y, Ichijima M, Lou Z, Nussenzweig A, Camerini-Otero RD, Chen J, Andreassen PR, Namekawa SH. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 2011 May 1;25(9):959-71.

Joo-Seop Park, PhD

is interested in understanding how progenitor cells maintain their multi-potent status and how they differentiate into different types of cells during organogenesis of the mammalian kidney and bladder. His lab studies transcriptional and epigenetic controls of cis-regulatory modules that act downstream of various signaling pathways.

Visit the Park Lab.

513-803-7871 pedsurology@cchmc.org

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Joo-Seop Park, PhD

Academic Affiliations

Assistant Professor, UC Department of Surgery

Phone 513-803-7871

Email pedsurology@cchmc.org

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Molecular biology; genetics.

Visit the Park Lab.

Biography

Joo-Seop Park, PhD, is an assistant professor in the Divisions of Pediatric Urology and Developmental Biology at Cincinnati Children's Hospital Medical Center. He received his bachelor's in pharmacy from Seoul National University in Seoul, South Korea. He subsequently studied the regulation of gene transcription with Dr. Jeffrey W. Roberts at Cornell University in Ithaca, NY where he obtained his doctorate in molecular biology and genetics in 2004. Dr. Park then went on to postdoctoral training with Dr. Andrew P. McMahon at Harvard University where he was awarded fellowships from the National Kidney Foundation and the Charles King Trust to study mammalian kidney development.

Dr. Park is interested in understanding how progenitor cells maintain their multi-potent status and how they differentiate into different types of cells during organogenesis of the mammalian kidney and bladder. His lab studies transcriptional and epigenetic controls of cis-regulatory modules that act downstream of various signaling pathways.

PhD: Molecular Biology, Cornell University.

Brunskill EW, Park JS, Chung E, Chen F, Magella B, Potter SS. Single cell dissection of early kidney development: multilineage priming. Development. 2014;141, 3093-3101.

Xu J, Liu H, Park JS, Lan Y, Jiang R. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis. Development. 2014;141, 1442-1452.

Wang J, Park JS, Wei Y, Rajurkar M, Cotton JL, Fan Q, Lewis BC, Ji H, Mao J. TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPalpha function. Mol Cell. 2013;51, 211-225.

Park JS, Ma W, O'Brien LL, Chung E, Guo JJ, Cheng JG, Valerius MT, McMahon JA, Wong WH, McMahon AP. Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell. 2012;23, 637-651.

Park JS, Valerius MT, McMahon AP. Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development. Development. 2007;134, 2533-2539.

Park JS, Roberts JW. Role of DNA bubble rewinding in enzymatic transcription termination. Proc Natl Acad Sci U S A. 2006;103, 4870-4875.

Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Developmental cell. 2005;9, 283-292.

Roberts J, Park, JS. Mfd, the bacterial transcription repair coupling factor: translocation, repair and termination. Current opinion in microbiology. 2004;7, 120-125.

Park JS, Marr MT, Roberts JW. E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell. 2002;109, 757-767.

S. Steven Potter, PhD

is interested in kidney and craniofacial development and disease. He uses a combination of laser capture microdissection, microarrays, and next generation sequencing, applied to both mouse models and human biopsy disease samples.
Visit the Potter Lab.

513-636-4850 steve.potter@cchmc.org

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S. Steven Potter, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4850

Fax 513-636-4317

Email steve.potter@cchmc.org

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Kidney development and disease; Hox genes; craniofacial development; creation of an atlas of global gene expression patterns in the multiple compartments of the developing kidney; analysis of perturbed gene expression patterns in the kidney glomeruli of patients with focal segmental glomerulosclerosis; craniofacial development using mutant mice, laser capture microdissection, next generation sequencing, and microarrays; recombineering to target multiple Hox genes at once

Visit the Potter Lab.

BA: University of California, Los Angeles (UCLA), CA, 1971.

PhD: University of North Carolina, Chapel Hill, NC, 1976.

Postdoctoral Fellowship: Harvard Medical School, Boston, MA, 1976-1978.

Potter SS, Brunskill EW, Patterson LT. Defining the genetic blueprint of kidney development. Pediatr Nephrol. 2011 Feb 19.

Potter SS, Brunskill EW, Patterson LT. Microdissection of the gene expression codes driving nephrogenesis. Organogenesis. 2010 Oct-Dec;6(4):263-9.

Brunskill EW, Potter SS. Gene expression programs of mouse endothelial cells in kidney development and disease. PLoS One. 2010 Aug 10;5(8):e12034.

Georgas K, Rumballe B, Valerius MT, Chiu HS, Thiagarajan RD, Lesieur E, Aronow BJ, Brunskill EW, Combes AN, Tang D, Taylor D, Grimmond SM, Potter SS, McMahon AP, Little MH. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol. 2009 332(2):273-86.

Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, Kaimal V, Jegga AG, Yu J, Grimmond S, McMahon AP, Patterson LT, Little MH, Potter SS. Atlas of gene expression in the developing kidney at microanatomic resolution. Dev Cell. 2008 Nov;15(5):781-91. Erratum in: Dev Cell. 2009 Mar;16(3):482. Yu, Jing [added].

Adam M, Murali B, Glenn NO, Potter SS. Epigenetic inheritance based evolution of antibiotic resistance in bacteria. BMC Evol Biol. 2008 Feb 18;8:52.

Bennett MR, Czech KA, Arend LJ, Witte DP, Devarajan P, Potter SS. Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli. Nephron Exp Nephrol. 2007;107(1):e30-40.

Potter SS, Hartman HA, Kwan KM, Behringer RR, Patterson LT. Laser capture-microarray analysis of Lim1 mutant kidney development. Genesis. 2007 Jul;45(7):432-9.

Song N, Schwab KR, Patterson LT, Yamaguchi T, Lin X, Potter SS, Lang RA. pygopus 2 has a crucial, Wnt pathway-independent function in lens induction. Development. 2007 May;134(10):1873-85.

Schwab KR, Patterson LT, Hartman HA, Song N, Lang RA, Lin X, Potter SS. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol. 2007 Apr 10;5:15.

Schwab K, Hartman HA, Liang HC, Aronow BJ, Patterson LT, Potter SS. Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development. Dev Biol. 2006 May 15;293(2):540-54.

Rolf W. Stottmann, PhD

is a developmental geneticist with an interest in using animal models to understand the genetic basis of human congenital defects. His lab is using both forward and reverse genetics to identify novel loci required for normal development. Further studies are then done to study the underlying molecular mechanism(s) leading to the defect. Specific areas of interest are cortical neuron development and craniofacial genetics.
Visit the Stottmann Lab.

513-636-7136 rolf.stottmann@cchmc.org

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Rolf W. Stottmann, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-7136

Email rolf.stottmann@cchmc.org

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Developmental neurobiology; genetics; animal models of human congenital defects

Visit the Stottmann Lab.

BS: University of Maryland, College Park, MD, 1995.

MS: University of Maryland, College Park, MD, 1997.

PhD: Duke University School of Medicine, Durham, NC, 2004.

Postdoctoral Training: Brigham & Women’s Hospital; Harvard Medical School.

Stottmann RW, Turbe-Doan A, Tran P, Kratz L, Moran J, Kelley R, Beier DR. Cholesterol metabolism is required for intracellular hedgehog signal transduction in vivo. PLoS Genetics. 2011.

Stottmann RW, Moran J, Turbe-Doan A, Driver E, Kelly M, Beier DR. An ENU screen for neurodevelopmental mutations in the mouse. Genetics. 2011 Jul;188(3):615-24.

Stottmann RW, Klingensmith J. Bone morphogenetic protein signaling is required in the dorsal neural folds before neurulation for the induction of spinal neural crest cells and dorsal neurons. Dev Dyn. 2011 Apr;240(4):755-65.

Stottmann RW, Beier DR. Using ENU mutagenesis for phenotype-driven analysis of the mouse. Methods Enzymol. 2010;477:329-48.

Stottmann RW, Bjork BC, Doyle JB, Beier DR. Identification of a Van der Woude syndrome mutation in the cleft palate 1 mutant mouse. Genesis. 2010 May;48(5):303-8.

Stottmann RW, Tran PV, Turbe-Doan A, Beier DR. Ttc21b is required to restrict sonic hedgehog activity in the developing mouse forebrain. Dev Biol. 2009 Nov 1;335(1):166-78.

Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008 Apr;40(4):403-10.

Stottmann RW, Berrong M, Matta K, Choi M, Klingensmith J. The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol. 2006 Jul 15;295(2):647-63.

Stottmann RW, Choi M, Mishina Y, Meyers EN, Klingensmith J. BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Development. 2004 May;131(9):2205-18.

Stottmann RW, Anderson RM, Klingensmith J. The BMP antagonists Chordin and Noggin have essential but redundant roles in mouse mandibular outgrowth. Dev Biol. 2001 Dec 15;240(2):457-73.

Saulius Sumanas, PhD

utilizes zebrafish as a model system to study molecular mechanisms of the embryonic vasculature formation.
Visit the Sumanas Lab.

513-803-0435 saulius.sumanas@cchmc.org

Joshua S. Waxman, PhD

uses genetic, molecular and cellular biological techniques to understand the underlying mechanisms of congenital heart defects and cardiomyocyte formation during development.
Visit the Waxman Lab.

513-636-7232 joshua.waxman@cchmc.org

Matthew T. Weirauch, PhD

is a computational biologist. His lab seeks to understand the mechanisms of gene transcriptional regulation. Current projects focus on characterizing transcription factor binding specificities, and developing methods for modeling their interactions with DNA, both in vitro and in vivo. His lab applies insights from basic research on transcription factor-DNA interactions to study the mechanisms underlying complex diseases.

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513-803-9078 matthew.weirauch@cchmc.org

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Matthew T. Weirauch, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-9078

Email matthew.weirauch@cchmc.org

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Transcription factors; transcriptional regulation; functional genomics; genome analysis

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Biography

Matthew T. Weirauch, PhD, a faculty member in the Center for Autoimmune Genomics and Etiology (CAGE), is a computational biologist with special emphasis on genomic approaches for studying transcription factor (TF) interactions with DNA, and how genetic variation proximal to these interactions contributes to human diseases. He recently spearheaded large-scale efforts for the experimental and computational determination of sequence binding motifs for eukaryotic TFs (Weirauch et al., Cell, 2014), and RNA binding proteins (Nature co-first author, 2013). He has also been involved in numerous high-profile genomics efforts, including an evaluation of algorithms for TF-DNA recognition (Weirauch et al., Nature Biotech, 2013), and the largest genetic interaction studies performed to date in both C. elegans (Byrne et al., Journal of Biology, 2007) and S. cerevisiae (Costanzo et al., Science, 2010). Recent work in his group focuses on how disease-associated genomic regions affect TF binding, and how these alterations affect disease onset and progression (Wang et al., Mol Cancer., 2010; Qian et al., Pediatr Blood Cancer, 2014; Kottyan et al., Nature Genetics, 2014; Martin et al., Circulation: Cardiovascular Genetics, 2014; Fang et al., Cell Reports, 2014).

The long-term goal of Dr. Weirauch's lab is to create an accurate computational system for predicting TF and RNA binding protein interactions with the genome/transcriptome, and for understanding the effects of genetic variations on these interactions. As it continues to mature, they are applying this system to predict the effects of genetic variants that are strongly associated with several human diseases. Long-term, they envision that this system will be used for personalized medicine-based approaches – given the genome sequence of a patient, it will produce a prioritized list of genetic variants likely to contribute to disease onset via alterations to protein binding events.

Postdoctoral Fellow: University of Toronto (Donnelly Center for Cellular and Biomolecular Research), Toronto, Ontario, Canada.

PhD: Bioinformatics, University of California Santa Cruz, Santa Cruz, California.

BSc: Computer Science, Pennsylvania State University, University Park, PA.

Weirauch M, Yang A, Albu M, Cote A, Montenegro-Montero A, Drewe P, Najafabadi H, Lambert S, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano J, Galli M, Lewsey M, Huang E, Mukherjee T, Chen X, Reece-Hoyes J, Govindarajan S, Shaulsky G, Walhout AJM, Bouget F, Ratsch G, Larrondo L, Ecker J, Hughes T. Determination and inference of eukaryotic transcription factor sequence specificity. Cell. 2014 Sep 11;158(6):1431-1443.

Makashir S, Kottyan L, Weirauch M. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing. 2014.

Kottyan L, Davis B, Sherrill J, Lui K, Rochman M, Kaufman K, Weirauch M, Vaughn S, Lazaro S, Rupert A, Kohram M, Stucke E, Kemme K, Magnusen A, He H, Dexheimer P, Mukkada V, Putnam P, Strauss A, Abonia JP, Martin L, Harley J, Rothenberg M. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet. 2014 Aug;46(8):895-900.

Sullivan A, Arsovski A, Lempe J, Bubb K, Weirauch M, et al. Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A. thaliana. Cell Reports. 2014 Sep 10.

Kottyan L, Zoller E, Bene J, Lu X, Kelly J, Rupert A, Lessard C, Vaughn S, Marion M, Weirauch M, et al. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet. 2014 Sep 8.

Weirauch M, Cote A, Norel R, Annala M, Zhao Y, Riley T, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S, DREAM5 Consortium, et al. Evaluation of methods for modeling transcription factor sequence specificity. Nature Biotechnology. 2013 Jan 27;31(2):126-34.

Ray D*, Kazan H*, Cook K*, Weirauch M*, Najafabadi H*, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat L, Dale R, Smith S, Yarosh C, Kelly S, Nabet B, Mecenas D, Li W, Laishram R, Qiao M, Lipshitz H, Piano F, Corbett A, Carstens R, Frey B, Anderson R, Lynch K, Penalva L, Lei E, Fraser A, Blencowe B, Morris Q, Hughes T. A compendium of RNA binding motifs for decoding gene regulation. Nature. 2013 Jul 10;499(7457):172-177. *co-first authors.

Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear E, Sevier C, Ding H, Koh J, Toufighi K, Mostafavi S, Prinz J, St Onge R, VanderSluis B, Makhnevych T, Vizeacoumar F, Alizadeh S, Bahr S, Brost R, Chen Y, Cokol M, Deshpande R, Li Z, Lin Z, Liang W, Marback M, Paw J, San Luis B, Shuteriqi E, Tong A, van Dyk N, Wallace I, Whitney J, Weirauch M, Zhong G, Zhu H, Houry W, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth F, Giaever G, Nislow C, Troyanskaya O, Bussey H, Bader G, Gingras A, Morris Q, Kim P, Kaiser C, Myers C, Andrews B, Boone C. The genetic landscape of a cell. Science. 2010 Jan 22;327(5964):425-31.

Byrne A, Weirauch M, Wong V, Koeva M, Dixon S, Stuart J, Roy P. A global analysis of genetic interactions in Caenorhabditis elegans. J Biol. 2007;6(3):8.

ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007 Jun 14;447(7146):799-816.

Grants

Viral transcription factor interactions with disease-associated genetic variants. Principal Investigator. Trustee Award, Cincinnati Children's. Jul 2014-Jun 2016.

Translational Genomics Analysis Core. Co-Investigator. NIH/NCRR CCTST T1 Pilot, Cincinnati Children's. Jul 2014-Jun 2016.

Decoding C2H2 Zinc Fingers. Collaborator. Canadian Institutes of Health Research (CIHR) Operating Grant. Oct 2013-Sep 2016.

James M. Wells, PhD Director, Basic Research, Division of Endocrinology

researches the molecular mechanisms of endoderm organogenesis in mouse and humans. The goal of this work is to identify the molecular basis of congenital defects affecting the pancreas, liver, and biliary system and to direct the differentiation of pluripotent stem cells (PSCs) into therapeutic cells for replacement therapies, such as transplantable pancreatic beta cells for patients with type-1 diabetes.
Visit the Wells Lab.

513-636-8767 james.wells@cchmc.org

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James M. Wells, PhD

Director, Basic Research, Division of Endocrinology

Director, Pluripotent Stem Cell Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8767

Fax 513-636-4317

Email james.wells@cchmc.org

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Research

Understanding the development of the pancreas, and gastrointestinal organs; generating 3-dimensional human tissues from pluripotent stem cells and using these as human models of diabetes and digestive disease.

For more information, please visit the Wells lab web page.

Biography

The focus of his teams basic research has been to identify the molecular mechanisms involved in the embryonic development of endocrine cells including pancreatic beta cells and tissues of the gastrointestinal tract. Their translational projects have focused on identifying new approaches to improve child health in several ways: 1. To identify and use embryonic pathways to generate complex, three-dimensional organ tissues from pluripotent stem cells, 2. Use these tissues to develop new in vitro human models for diabetes and digestive disease research and 3. Develop long-term, therapeutic strategies for cell and tissue-replacement therapies.

BS: Biochemistry, Molecular and Cell Biology, University of Maine, Orono, ME, 1987.

PhD: Graduate program in Genetics, SUNY at Stony Brook, New York, 1995.

Postdoctoral Fellow: Harvard University, Cambridge MA, 1996 - 2001.

View Dr. Wells PubMed Publications.

McCracken KW, Catá E, Crawford C, Sinagoga KL, Schumacher M, Mayhew CN, Zavros Y, Wells JM. Modelling human development and disease in pluripotent stem cell-derived gastric organoids. Nature. 2014 Dec 18;516(7531):400-4.

Watson CL, Mahe MM, Howell JC, Munera J, Sundaram N, Schweitzer J, Vallance JE, Shroyer NF, Wells JM, Helmrath MA. An in vivo model of human small intestine using pluripotent stem cells. Nat Med. 2014 Nov;20(11):1310-4.

Ji H, Zhang X, Oh S, Mayhew C, Ulm A, Somineni H, Ericksen M, Wells J, Khurana Hershey GK. Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells. J Allergy Clin Immunol. 2014 Oct 14, pii:S0091-6749(14)01262-7.

Chlon TM, Hoskins EE, Mayhew CN, Wikenheiser-Brokamp KA, Davies SM, Mehta P, Myers KC, Wells JM, Wells, SI. High-Risk Human Papillomavirus E6 Protein Promotes Reprogramming of Fanconi Anemia Patient Cells through Repression of p53 but Does Not Allow for Sustained Growth of Induced Pluripotent Stem Cells. J Virol. 2014 Oct 1;88(19)11315-26.

Jonatan D, Spence JR, Method AM, Sinagoga K, Kofron M, Haataja L, Arvan P, Deutsch GH, Wells JM. Sox17 regulates insulin secretion in the normal and pathologic beta cell. PLoS One. 2014 Aug 21;9(8):e104675.

Schiesser JV, Wells JM. Generation of beta cells from human pluripotent stem cells: are we there yet? Ann N Y Acad Sci. 2014 Apr;1311:124-37.

Runck LA, Method A, Bischoff A, Levitt M, Peña A, Collins MH, Gupta A, Shanmukhappa S, Wells JM, Guasch G. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human. Dis Model Mech. 2014 Apr;7(4):483-93.

Wells JM, Spence JR. How to make an intestine. Development. 2014 Feb;141(4):752-60.

Delgiorno KE, Hall JC, Takeuchi KK, Pan FC, Halbrook CJ, Washington MK, Olive KP, Spence JR, Sipos B, Wright CV, Wells JM, Crawford HC. Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology. 2014 Jan;146(1):233-44.e5.

Suissa Y, Magenheim J, Stolovich-Rain M, Hija A, Collombat P, Mansouri A, Sussel L, Sosa-Pineda B, McCracken K, Wells JM, Heller RS, Dor Y, Glaser B. Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas. PLoS One. 2013 Aug 5;8(8):e70397.

Grants

Investigation of regional identity in human intestinal stem cells. Principal investigator (along with Shroyer NF, PI and Helmrath M, PI). National Institutes of Health. Sep 2014 – Aug 2019. NIH U01DK103117.

Single Cell Dissection of Human Intestine Development. Principal Investigator. National Institutes of Health. Sep 2013 – Aug 2018. NIH 1R01DK098350.

Control of human endocrine cell development. Contact Principal Investigator. National Institutes of Health. Apr 2012 – Mar 2017. NIH 1R01DK092456-01.

Transcriptional Control of Placental Differentiation. Co-Investigator. National Institutes of Health. Feb 2011 – Jan 2016. NIH R01 HD065339.

Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute

513-803-2790 jeffrey.whitsett@cchmc.org

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Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy

Visit the Whitsett Lab.

Biography

Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.

Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.

MD: Columbia University, New York, NY, 1973.

Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.

Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.

Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.

Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.

Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.

Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.

Chunyue Yin, PhD

studies the cellular and molecular basis of liver development and disease pathogenesis. She focuses on hepatic stellate cells, the key cell type responsible for hepatic fibrogenesis. She utilizes the zebrafish model to investigate the regulation of hepatic stellate cells during liver development and alcoholic liver injury, and their function in liver regeneration. Research in congenital biliary diseases is a second lab focus.

Visit the Yin Lab.

513-803-8096 chunyue.yin@cchmc.org

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Chunyue Yin, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-8096

Email chunyue.yin@cchmc.org

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Liver development; hepatic fibrosis and cirrhosis; hepatic stellate cells; stem cells and regeneration; congenital biliary diseases; zebrafish genetics

Visit the Yin Lab.

Biography

Dr. Yin conducted her doctoral research in Dr. Lilianna Solnica-Krezel’s laboratory at Vanderbilt University, where she investigated the molecular regulation of cell movements during zebrafish gastrulation and revealed the impact of gastrulation movements on somite development. In parallel, she participated in a forward genetic screen to identify novel regulators of zebrafish early development. She identified the calamity mutant that exhibits defects in notochord formation and pigmentation. Subsequent positional cloning revealed that a mutation in the atp7a gene, the zebrafish homolog of the human Menkes disease gene, was responsible for the calamity mutant phenotypes.

With a strong interest in building zebrafish models for human diseases, she decided to conduct her postdoctoral research in Dr. Didier Stainier’s laboratory, which is at the forefront of zebrafish digestive organ research. She received a postdoctoral fellowship from the Juvenile Diabetes Research Foundation to study pancreas development in zebrafish hands-off/han mutants that carry a mutation in the transcription factor gene hand2. Her research led to the discovery that the defective pancreatic development in han mutants is due to a failure in asymmetric gut looping. She also showed that gut-looping morphogenesis is dependent on extracellular matrix remodeling and revealed novel roles for Hand2 in this process. This work was published in Developmental Cell in 2010. Her work is now focused on the hepatic stellate cells and hepatic biliary cells. She has developed transgenic lines that mark these cell types and will use them and related reagents to characterize the cellular behaviors of these cells in liver development and disease, as well as the underlying molecular regulations.

BS: Evolution and Ecology, Fudan University, Shanghai, China, 2001.

PhD: Developmental Biology, Vanderbilt University, Nashville, TN, 2007.

Postdoctoral fellow: Developmental Biology, University of California at San Francisco, San Francisco, CA, 2012.

View PubMed publications

Delous M*, Yin C*, Shin D, Ninov N, Carten JD, Pan L, Ma TP, Farber SA, Moens CB, Stainier DYR. Sox9b is a key regulator of pancreaticobiliary ductal system development. PLoS Genetics. 2012. * These authors contribute equally to this work.

Yin C*, Evason K, Maher JJ, Stainier DYR. The bHLH transcription factor Hand2 marks hepatic stellate cells in zebrafish: analyses of stellate cell entry into the developing liver. Hepatology. 2012. * Co-corresponding author.

Yin C, Kikuchi K, Hochgreb T, Poss KD, Stainier DYR. Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish. Developmental Cell. 2010;18: 973-984.

Yin C, Kiskowski M, Pouille PA, Farge E, Solnica-Krezel L. Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation. J Cell Biol. 2008;180: 221-232.

Yin C, Solnica-Krezel L. Convergence and extension movements affect dynamic notochord-somite interactions essential for zebrafish slow muscle morphogenesis. Dev Dyn. 2007;236: 2742-2756.

Yin C, Solnica-Krezel L. Convergence and extension movements mediate the specification and fate maintenance of zebrafish slow muscle precursors. Dev Biol. 2007;304(1): 141-155.

Mendelsohn B*, Yin C*, Wilm T, Johnson S, Solnica-Krezel L, Gitlin J. Atp7a determines a hierarchy of copper metabolism during embryogenesis essential for notochord development. Cell Metabolism. 2006;4(2):155-62. * These authors contributed equally to this work.

Lin F, Sepich DS, Chen S, Topczewski J, Yin C, Solnica-Krezel L, Hamm H. Essential roles of Gα12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements. J Cell Biol. 2005;169(5): 777-787.

Marlow F, Gonzalez EM, Yin C, Rojo C, Solnica-Krezel L. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish. Development. 2004;131(1): 203-216.

Yin C, Qian J, Fu C, Ma Y, Zheng S, Mao Y. Genetic diversity in natural populations of glycine tabacina in Fujian, China. J Gen Mol Biol. 2002;13: 6-12.

Yutaka Yoshida, PhD

investigates the molecular mechanisms of neural circuit formation in the developing spinal cord, using many techniques including molecular biology, mouse genetics, biochemistry, and electrophysiology.
Visit the Yoshida Lab.

513-803-0943 yutaka.yoshida@cchmc.org

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Yutaka Yoshida, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-0943

Email yutaka.yoshida@cchmc.org

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Molecular mechanisms of neural circuit formation in the developing spinal cord.

Visit the Yoshida Lab.

BS: Keio University, 1994.

PhD: University of Tokyo, 1999.

Postdoctoral fellow: University of Tokyo, 1999-2002; Columbia University, 2002-2007.

Fukuhara K, Imai F, Ladle DR, Katayama K, Leslie JR, Arber S, Jessell TM, Yoshida Y. Specificity of monosynaptic sensory connections imposed by repellent sema3e-plexinD1 signaling. Cell Rep. 2013 Nov 14;5(3):748-58.

Katayama K, Imai F, Campbell K, Lang RA, Zhneg Y, Yoshida Y. RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic eminence ventricular zone for proper cortical interneuron migration. Development. 2013 Aug;140(15):3139-45.

Katayama K, Leslie JR, Lang RA, Zheng Y, Yoshida Y. Left-right locomotor circuitry depends upon RhoA-driven organization of the neuroepithelium in the developing spinal cord. Journal of Neuroscience. 2012 Jul 25;32(30):10396-407.

Leslie JR, Imai F, Fukuhara K, Takegahara N, Rizvi TA, Friedel RH, Wang F, Kumanogoh A, Yoshida Y. Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of changing semaphorin6D signaling inhibit synapse formation. Development. 2011.

Katayama K, Melendez J, Baumann JM, Leslie JR, Chauhan BK, Nemkul N, Lang RA, Kuan CY, Zheng Y, Yoshida Y. Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7607-12.

Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, and Arber S. Specificity of Monosynaptic Sensory-Motor Connections Encoded by Sema3e-PlexinD1. Nature. 2009 459:842-6.

Yoshida Y, Han B, Mendelsohn M, Jessell TM. PlexinA1 signaling directs the segregation of proprioceptive sensory axons in the developing spinal cord. Neuron. 2006 52:775-88.

Gu C*, Yoshida Y*, Livet J., Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science. 2005 307:265-8. (* denotes equal contribution)

Yoshida Y, Nakamura T, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003 17:1201-6.

Yoshida Y, Tanakam S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell. 2000 103:1085-97.

Aaron M. Zorn, PhD Associate Director, Digestive Health Center

leads the Zorn lab with the research goal to understand the development of the lung, liver, pancreas and gastrointestinal tract, which are derived from the embryonic endoderm. We use frog embryos to investigate the genetic pathways underlying the process of organogenesis. The research in this Lab helps our understanding of congenital diseases in these organs and the ability to development stem cells therapies.
Visit the Zorn Lab.

513-636-3770 aaron.zorn@cchmc.org

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Aaron M. Zorn, PhD

Associate Director, Digestive Health Center

Co-Director, Xenbase

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3770

Fax 513-636-4317

Email aaron.zorn@cchmc.org

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Development of lung, liver, pancreas and gastrointestinal tract; vertebrate embryology

Visit the Zorn Lab.

BSc: University of Toronto, Canada.

PhD: University of Texas, Austin, Texas, 1995.

Postdoctoral: Wellcome Trust Cancer Research Campaign Institute, University of Cambridge, Cambridge, England, 1996-1999.

Research Fellow: Wellcome Trust Gurdon Institute, Universtiy of Cambridge, Cambridge, England, 1999-2002.

Nolan K, Kattamuri C, Luedeke D, Deng A, Jagpal A, Zhang F, Linhardt R, Kenny AP, Zorn AM, Thompson TB. Structure of Protein Related to DAN and Cerberus (PRDC): Insights into the Mechanism of BMP Antagonism. Structure. 2013 Aug 6;21(8):1417-29.

Zhang Z, Rankin, SA, Zorn AM. Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endodermal progenitor cells. Dev Bio. 2013 Jun 1;378(1):1-12.

Bowes JB, Snyder KA, James-Zorn C, Ponferrada VG, Jarabek CJ, Burns KA, Bhattacharyya B, Zorn AM, Vize PD. The Xenbase literature curation process. Database (Oxford).2013 Jan 9;2013:bas046.

James-Zorn C, Ponferrada VG, Jarabek CJ, Burns KA, Segerdell EJ, Lee J, Snyder K, Bhattacharyya B, Karpinka JB, Fortriede J, Bowes JB, Zorn AM, Vize PD. Xenbase: expansion and updates of the Xenopus model organism database. Nucleic Acids Res. . 2013 Jan;41:D865-70.

Kattamuri C, Luedeke DM, Nolan K, Rankin SA, Greis KD, Zorn AM, Thompson TB. Members of the DAN Family are BMP Antagonists that form Highly Stable Noncovalent Dimers. J Mol Biol. 2012 Dec 14;424(5):313-27.

Shifley ET, Kenny AP, Rankin SA, Zorn AM. Prolonged FGF signaling is necessary for lung and liver induction in Xenopus. BMC Dev Bio. 2012 Sep 18;12:27.

Kenny AP, Rankin SA, Allbee AW, Prewitt AR, Zhang Z, Shifley E, Louza M, Zorn AM. Sizzled-Tolloid interactions maintain foregut progenitors by regulating Fibronectin-dependent BMP signaling. Dev Cell. 2012 Aug 14;23(2):292-304.

Rankin SA, Neto A, Gallas A, Gómez-Skarmeta JL, Zorn AM. Suppression of Bmp4 signaling by the zinc-finger repressors Osr1 and Osr2 is required for Wnt/beta-catenin-mediated lung specification in Xenopus. Development. 2012 Aug;139:3010-20.

Ponferrada VG, Fan J, Vallance JE, Hu S, Mamedova A, Rankin SA, Kofron M, Zorn AM, Hegde RS, Lang RA. CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis. PLoS One. 2012;7(3):e32635.

Rankin SA, Zorn AM, Buchholz RD. New doxycycline-inducible transgenic lines in Xenopus. Dev Dyn. 2011 June;240(6):1467-74.

Rankin SA, Kormish J, Jegga, A Kofron M, Zorn AM. A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer. Dev Bio. 2011 Mar 15;351(2):297-310.

Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 2011. Feb 3;470:105-9.

Grants

Deciphering the gene regulatory network controlling vertebrate endodermal fates. Co-Principal Investigator. National Institutes of Health. July 2012 - June 2017. #R01 HD73179.

Role of Osr transcription factors in lung specification. Principal Investigator. National Institutes of Health. July 2012 - June 2017. #R01 HL114898.

Production, Validation and Distribution of the Xenopus ORFeome. Co-Investigator. National Institutes of Health. July 2011 - June 2016. #R01 HD069352A.

Section Chief

Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute

513-803-2790 jeffrey.whitsett@cchmc.org

High Res

Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

Show All

Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy

Visit the Whitsett Lab.

Biography

Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.

Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.

MD: Columbia University, New York, NY, 1973.

Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.

Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.

Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.

Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.

Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.

Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.

Faculty

Henry T. Akinbi, MD Attending Neonatologist, Neonatology and Pulmonary Biology

studies host defense proteins in innate defense of the lungs using gene-targeted mice. The role of lysozyme in: 1) lung infection; 2) inflammation and 3) anti-oxidant defense is a major focus of his research program.

513-636-8915 henry.akinbi@cchmc.org

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Henry T. Akinbi, MD

Attending Neonatologist, Neonatology and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8915

Fax 513-636-7868

Email henry.akinbi@cchmc.org

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Clinical

Neonatal infections; blood transfusions

Research

Role of lysozyme in airway host defense

MD: University of Ife, Ile-Ife, Nigera, Africa, 1980.

Residency: Pediatrics, University of North Carolina at Chapel Hill, 1988-1991.

Neonatology Fellowship: Children's Hospital of Philadelphia, Philadelphia, PA, 1991-1994.

Certification: General Pediatrics, 1991; Recertification, 1998; Newborn Medicine, 1995; Recertification, 2002.

McDowell SA, Ma Y, Kusano R, Akinbi HT. Simvastatin is Protective During Staphylococcus aureus Pneumonia. Curr Pharm Biotechnol. 2011 Mar 14.

Kuang Z, Hao Y, Hwang S, Zhang S, Kim E, Akinbi HT, Schurr MJ, Irvin RT, Hassett DJ, Lau GW. The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing. Mol Microbiol. 2011 Mar;79(5):1220-35.

Isemann B, Meinzen-Derr J, Akinbi H. Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome. J Perinatol. 2011 Jan;31(1):25-9.

Slaughter JL, Meinzen-Derr J, Rose SR, Leslie ND, Chandrasekar R, Linard SM, Akinbi HT. The effects of gestational age and birth weight on false-positive newborn-screening rates. Pediatrics. 2010 Nov;126(5):910-6.

Akinbi H, Meinzen-Derr J, Auer C, Ma Y, Pullum D, Kusano R, Reszka KJ, Zimmerly K. Alterations in the host defense properties of human milk following prolonged storage or pasteurization. J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):347-52.

Yang L, Johansson J, Ridsdale R, Willander H, Fitzen M, Akinbi HT, Weaver TE. Surfactant protein B propeptide contains a saposin-like protein domain with antimicrobial activity at low pH. J Immunol. 2010 Jan 15;184(2):975-83.

Glasser SW, Witt TL, Senft AP, Baatz JE, Folger D, Maxfield MD, Akinbi HT, Newton DA, Prows DR, Korfhagen TR. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L64-72.

Walker VP, Akinbi HT, Meinzen-Derr J, Narendran V, Visscher M, Hoath SB. Host defense proteins on the surface of neonatal skin: implications for innate immunity. J Pediatr. 2008 Jun;152(6):777-81.

Nash JA, Ballard TN, Weaver TE, Akinbi HT. The peptidoglycan-degrading property of lysozyme is not required for bactericidal activity in vivo. J Immunol. 2006 Jul 1;177(1):519-26

Ryan MA, Akinbi HT, Serrano AG, Perez-Gil J, Wu H, McCormack FX, Weaver TE. Antimicrobial activity of native and synthetic surfactant protein B peptides. J Immunol. 2006 Jan 1;176(1):416-25.

Tanya E. Cahill, MD Director, High-Risk Clinic

is interested in high risk infant follow-up and neonatal abstinence syndrome.

tanya.cahill@cchmc.org

Michael W. Crossman, MD, PhD Attending Neonatologist, Neonatology and Pulmonary Biology

focuses on intestinal function and host-microbial interactions, bioethics and neonatal palliative care.

859-301-3850 michael.crossman@cchmc.org

High Res

Michael W. Crossman, MD, PhD

Attending Neonatologist, Neonatology and Pulmonary Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 859-301-3850

Fax 859-301-2066

Email michael.crossman@cchmc.org

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Intestinal function and host-microbial interactions; bioethics and neonatal palliative care

PhD: Biochemistry, St. Louis University, St. Louis, MO, 1985.

MD: St. Louis University, St. Louis, MO, 1986.

Residency: Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, 1986-1989; Chief resident, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 1989-1990.

Fellowship: Neonatal- Perinatal Medical Fellowship, Washington University School of Medicine, 1990-1993.

Certification: Neonatal - Perinatal Medicine, 1995, 2003.

Crossman MW. For Whom the Bells Toll… J Pediatrics. 2007;151(1):4-5.

Mishra A, Hogan SP, Brandt EB, Wagner N, Crossman MW, Foster PS, Rothenberg ME. Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J Biol Chem. 2002 Feb 8;277(6):4406-12.

Arrese M, Trauner M, Sacchiero RJ, Crossman MW, Scheider BL. Neither Intestinal Sequestration of Bile Acids nor Common Bile Duct Ligation Modulate the Expression and Function of the Rat Ileal Bile Acid Transporter. Hepatology. 1998;28:1081-1087.

Shneider BL, Setchell KDR, Crossman MW. Fetal and Neonatal Expression of the Apical Sodium-Dependent Bile Acid Transporter in the Rat Ileum and Kidney. Pediatric Research. 1997;42:189-194.

Stephan W. Glasser, PhD

studies the function of surfactant protein C (SP-C) in lung innate defense and as a cause of familial interstitial lung disease (ILD) in neonates and children. SP-C deficient mice, generated in his laboratory, exhibit features of human ILD and are susceptible to inflammation/bacterial and viral pulmonary infection. Experiments are focused on determining mechanisms underlying the role of SP-C deficiency in lung injury.

513-636-7850 steve.glasser@cchmc.org

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Stephan W. Glasser, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-7850

Fax 513-636-7868

Email steve.glasser@cchmc.org

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Clinical

Pulmonary biology: gene regulation in the lung

Research

Pulmonary surfactant protein C (SP-C) in lung innate defense; familial interstitial lung disease (ILD); deficiencies of SP-C; determining the mechanisms underlying the lung injury due to a lack of SP-C

PhD: University of Cincinnati, Developmental Biology,1988.

Hardie WD, Glasser SW, Hagood JS. Emerging concepts in the pathogenesis of lung fibrosis. Am J Pathol. 2009 Jul;175(1):3-16.

Glasser SW, Witt TL, Senft AP, Baatz JE, Folger D, Maxfield MD, Akinbi HT, Newton DA, Prows DR, Korfhagen TR. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L64-72.

Glasser SW, Senft AP, Whitsett JA, Maxfield MD, Ross GF, Richardson TR, Prows DR, Xu Y, Korfhagen TR. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice. J Immunol. 2008 Jul 1;181(1):621-8.

Glasser SW, Nogee LM. Genetically engineered mice in understanding the basis of neonatal lung disease. Semin Perinatol. 2006 Dec;30(6):341-9. Review.

Glasser SW, Eszterhas SK, Detmer EA, Maxfield MD, Korfhagen TR. The murine SP-C promoter directs type II cell-specific expression in transgenic mice. Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L625-32

Glasser SW, Detmer EA, Ikegami M, Na CL, Stahlman MT, Whitsett JA. Pneumonitis and emphysema in sp-C gene targeted mice. J Biol Chem. 2003 Apr 18;278(16):14291-8.

Ikegami M, Weaver TE, Conkright JJ, Sly PD, Ross GF, Whitsett JA, Glasser SW. Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury. J Appl Physiol. 2002 Feb;92(2):519-26.

Liu C, Glasser SW, Wan H, Whitsett JA. GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression. J Biol Chem. 2002 Feb 8;277(6):4519-25.

Whitsett JA, Glasser SW, Tichelaar JW, Perl AK, Clark JC, Wert SE. Transgenic models for study of lung morphogenesis and repair: Parker B. Francis lecture. Chest. 2001 Jul;120(1 Suppl):27S-30S.

Glasser SW, Burhans MS, Korfhagen TR, Na CL, Sly PD, Ross GF, Ikegami M, Whitsett JA. Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6366-71.

James M. Greenberg, MD Co-Director, Perinatal Institute

513-636-3149 james.greenberg@cchmc.org

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James M. Greenberg, MD

Co-Director, Perinatal Institute

Director, Division of Neonatology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3149

Fax 513-803-0968

Email james.greenberg@cchmc.org

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Neonatal chronic lung disease; late preterm infant

MD: University of Illinois College of Medicine, Chicago, IL, 1977-1981.

Certification: American Board of Pediatrics, 1988; subspecialty board, Neonatal/Perinatal Medicine, 1989.

Binder S, Hill K, Meinzen-Derr J, Greenberg JM, Narendran V. Increasing VLBW Deliveries at Subspecialty Perinatal Centers via Perinatal Outreach. Pediatrics. 2011 Mar;127(3):487-93.

Kulkarni RM, Herman A, Ikegami M, Greenberg JM, Akeson AL. Lymphatic ontogeny and effect of hypoplasia in developing lung. Mech Dev. 2011 Jan-Feb;128(1-2):29-40.

Kulkarni RM, Greenberg JM, Akeson AL. NFATc1 regulates lymphatic endothelial development. Mech Dev. 2009 May-Jun;126(5-6):350-65.

Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.

Preciado DA, Rutter MJ, Greenberg JM, Bahado-Singh R, Lambers D, Willging JP. Intrapartum management of severe fetal airway obstruction. J Otolaryngol. 2004 Oct;33(5):283-8.

Greenberg JM, Thompson FY, Brooks SK, Shannon JM, Akeson AL. Slit and robo expression in the developing mouse lung. Dev Dyn. 2004 Jun;230(2):350-60.

Beth E. Haberman, MD Senior Medical Director, Neonatal Services

has special interests in the care of infants with congenital diaphragmatic hernia and follow-up care of premature and term infants with complex medical needs.

513-636-5465 beth.haberman@cchmc.org

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Beth E. Haberman, MD

Senior Medical Director, Neonatal Services

Medical Director, Newborn Intensive Care Unit (NICU)

Medical Director, Neonatal Transport Program

Associate Director, High-Risk Infant Follow-Up Program

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-5465

Fax 513-636-5846

Email beth.haberman@cchmc.org

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CDH and infant follow-up; care of infants with congenital diaphragmatic hernia; follow-up care of premature and term infants with complex medical needs

Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 1996-1999.

Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1993-1996.

MD: University of Louisville, Louisville, KY, 1993.

Vuletin JF, Lim FY, Cnota J, Kline-Fath B, Salisbury S, Haberman B, Kingma P, Frischer J, Crombleholme T. Prenatal pulmonary hypertension index: novel prenatal predictor of severe postnatal pulmonary artery hypertension in antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg. 2010 Apr;45(4):703-8.

Greenberg JM, Donovan EF, Warner BB, Haberman BE, Narendran V, Schibler KR. Neonatal Morbidities of Prenatal and Perinatal Origin. Creasy and Resnik”s Maternal-Fetal Medicine: Principles and Practice. 2008 6th ed. Chapter 58. Elsevier Ltd., Philadelphia, PA.

Castro L, Yolton K, Haberman B, Roberto N, Hansen NI, Ambalavanan N, Vohr BR, Donovan EF. Bias in reported neurodevelopmental outcomes among extremely low birth weight survivors. Pediatrics. 2004 Aug;114(2):404-10.

Steven B. Hoath, MD

has varied research interests including epidermal barrier development (in utero and postnatal), fetal and neonatal skin adaptation (skin/environment interactions), tissue engineering of human skin (in vitro systems), innate immune function (biology of vernix and skin proteomics), development of non-invasive skin-based sensors for brain monitoring and the role of the skin as a critical interface for health care delivery.

513-803-0960 steven.hoath@cchmc.org

High Res

Steven B. Hoath, MD

Academic Affiliations

Emeritus, UC Department of Pediatrics

Phone 513-803-0960

Fax 513-803-0969

Email steven.hoath@cchmc.org

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Clinical

Human skin development; multiple roles of the skin in neonatal care; new perspectives on the skin as a sensory interface; role of the skin as an accessible environmental interface which complements ‘internal’ medicine; evidence-based organizational change in healthcare delivery to newborns; interface between medicine and nursing; focus on the bedside for the development of a truly “personalized” or “individualized” medicine in the future.

Research

Epidermal barrier development (in utero and postnatal); fetal and neonatal skin adaptation (skin/environment interactions); tissue engineering of human skin (in vitro systems); innate immune function (biology of vernix and skin proteomics); development of non-invasive skin-based sensors for brain monitoring; role of the skin as a critical interface for health care delivery.

Biography

Dr. Hoath graduated from Stanford University and the University of Hamburg, Germany with majors in biology and German studies. He received his MD from the University of California, Los Angeles and completed his pediatric residency and fellowship in neonatology at UCLA before joining Cincinnati Children’s Hospital Medical Center in 1984.

He has a longstanding interest in the development of fetal and newborn skin and the multiple roles of the skin as a critical interface for healthcare delivery in the NICU. In 1994, he was one of seven international investigators participating in the first joint effort by NASA and the National Institutes of Health to study the effect of spaceflight and zero gravity on mammalian pregnancy and fetal development. This work grounds the idea of the skin as the ‘biological spacesuit’ for the human body.

He has authored multiple papers, chapters, and a book on neonatal skin development. He is an inventor on five patents awarded to Cincinnati Children’s Hospital Medical Center based on the biology of the multifunctional fetal skin ‘cream’, vernix caseosa. Recent work has focused on the logico-mathematical organization of human epidermis and the close embryological connection of the skin and the brain.

Certification: American Board of Pediatrics, June 1983; Neonatal-Perinatal Medicine, November, 1983.

Adjunct Assistant Professor: Harbor UCLA Medical Center, Los Angeles, 1983.

Residency: University of California, Los Angeles, 1977-79.

Internship: Harbor-UCLA Medical Center, 1976-1977.

MD: University of California, Los Angeles, CA, 1976.

Fellowship: Neonatology, Harbor-UCLA, Los Angeles Medical Center, 1980-1982; Pathology, UCLA School of Medicine, 1973-1974.

Baccalaureate: Stanford University, Biology & German Studies, 1972.

Visscher MO, Robinson M, Fugit B, Rosenberg RJ, Hoath SB, Randall Wickett R. Amputee skin condition: occlusion, stratum corneum hydration and free amino acid levels. Arch Dermatol Res. 2010 Dec 16.

Davis JA, Visscher MO, Wickett RR, Hoath SB. Influence of tumour necrosis factor-α polymorphism-308 and atopy on irritant contact dermatitis in healthcare workers. Contact Dermatitis. 2010 Dec;63(6):320-32.

Davis JA, Visscher MO, Wickett RR, Hoath SB. Role of TNF-α polymorphism -308 in neurosensory irritation. Int J Cosmet Sci. 2010 Jul 15.

Narendran V, Visscher MO, Abril I, Hendrix SW, Hoath SB. Biomarkers of epidermal innate immunity in premature and full-term infants. Pediatr Res. 2010 Apr;67(4):382-6.

Barai ND, Boyce ST, Hoath SB, Visscher MO, Kasting GB. Improved barrier function observed in cultured skin substitutes developed under anchored conditions. Skin Res Technol. 2008 Nov;14(4):418-24.

Walker VP, Akinbi HT, Meinzen-Derr J, Narendran V, Visscher M, Hoath SB. Host defense proteins on the surface of neonatal skin: implications for innate immunity. J Pediatr. 2008 Jun;152(6):777-81.

Hoath SB, Pickens WL, Visscher MO. The biology of vernix caseosa. Int J Cosmet Sci. 2006 Oct;28(5):319-33.

Spitzmiller RE, Phillips T, Meinzen-Derr J, Hoath SB. Amplitude-integrated EEG is useful in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischemic encephalopathy: a meta-analysis. J Child Neurol. 2007 Sep;22(9):1069-78.

Tansirikongkol A, Hoath SB, Pickens WL, Visscher MO, Wickett RR. Equilibrium water content in native vernix and its cellular component. J Pharm Sci. 2008 Feb;97(2):985-94.

Tansirikongkol A, Wickett RR, Visscher MO, Hoath SB. Effect of vernix caseosa on the penetration of chymotryptic enzyme: potential role in epidermal barrier development. Pediatr Res. 2007 Jul;62(1):49-53.

Alan H. Jobe, MD, PhD Director, Division of Perinatal Biology

has a special research focus on surfactant physiology. Dr. Jobe is also interested in lung maturation and lung injury in the fetus and newborn, the use of antenatal corticosteroids, and lung injury with ventilation of the preterm infant.

513-636-8563 alan.jobe@cchmc.org

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Alan H. Jobe, MD, PhD

Director, Division of Perinatal Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8563

Fax 513-636-8691

Email alan.jobe@cchmc.org

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Clinical Interests

Clinical trials in neonatology; bronchopulmonary dysplasia

Research Interests

Lung maturation and lung injury in the fetus and newborn; use of antenatal corticosteroids; lung injury with ventilation of the preterm

MD: University of California, San Diego, CA, 1973.

PhD: University of California, San Diego, CA, 1973.

Residency: University Hospital, University of California, San Diego, CA, 1974 to 1975.

Fellowship: University of California, San Diego, CA, 1975 to 1977.

Board Certified: Pediatrics and Neonatal-Perinatal Medicine.

Moss TJM, Nitsos I, Knox CL, Polglase GR, Kallapur SG, Ikegami M, Jobe AH, Newnham JP. Ureaplasma colonization of amniotic fluid and efficacy of antenatal corticosteroids for preterm lung maturation in sheep. AJOG. 2009;200(1):96.e1-6.

Polglase GR, Hillman NH, Ball MK, Kramer BW, Kallapur SG, Jobe AH, Pillow JJ. Lung and systemic inflammation in preterm lambs on CPAP or conventional ventilation. Pediatr Res. 2009;65(1):67-71.

Cheah F-C, Pillow JJ, Kramer BW, Polglase GR, Nitsos I, Newnham JP, Jobe AH, Kallapur SG. Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis. Am J Physiol Lung Cell Mol Physiol. 2008;296:L384-93.

Ball MK, Jobe AH, Polglase GR, Kallapur SG, Choe-Cheah F, Hillman NH, Pillow JJ. High and low body temperature during the initiation of ventilation for near-term lambs. Resuscitation. 2008;80:133-7.

Kramer BW, Albertine KH, Moss TJM, Nitsos I, Speer CP, Newnham JP, Jobe AH. All-trans retinoic acid does not modulate intra-amniotic endotoxin mediated effects on the fetal sheep lung. The Anatomical Record. 2008;291:1271-7.

Polglase GR, Hillman NH, Pillow JJ, Cheah F-C, Nitsos I, Moss TJ, Kramer BW, Ikegami M, Kallapur SG, Jobe AH. Positive end-expiratory pressure and tidal volume during initial ventilation of preterm lambs. Pediatr Res. 2008;64:517.

Hillman N, Moss TJM, Nitsos I, Kramer BW, Bachurski C, Ikegami M, Jobe AH, Kallapur SG. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res. 2008;63:388-93.

Sweet DG, Huggett MT, Warner JA, Moss TJM, Halliday HL, Newnham JP, Kallapur SG, Jobe AH, Kramer BW. Maternal betamethasone and chorioamnionitis induce different collagenases and lung maturation in fetal sheep lungs. Neonatology. 2008;94:79-86.

Jobe AH, Moss TJM, Nitsos Il, Ikegami M, Kallapur SG, Newnham JP. Betamethasone for lung maturation: testing dose and formulation in fetal sheep. AJOG. 2007;197:523.

Moss TJM, Knox CL, Kallapur SG, Nitsos I, Theodoropoulos C, Ikegami M, Newnham JP, Jobe AH. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. Am J Ob Gyn. 2008;198:122e18.

Beth Ann Johnson, MD, MA Attending Neonatologist, Neonatology and Pulmonary Biology

has a research focus in perinatal cardiology, premature infants with congenital heart disease, fetal diagnosis, and simulation.

513-636-3291 beth_ann.johnson@cchmc.org

Tanya V. Kalin, MD, PhD

studies the transcriptional regulation of DNA replication and mitosis in tumor cells in vitro and in vivo. Mouse lung and prostate cancer models are used to gain insight into regulation of cell signaling pathways required for tumor initiation, progression, metastasis and tumor angiogenesis. The ultimate goal of the research program is to identify novel target genes for diagnostic, prevention and treatment of lung and prostate cancers.
Visit the Kalin Lab.

513-803-1201 tatiana.kalin@cchmc.org

High Res

Tanya V. Kalin, MD, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1201

Fax 513-636-2423

Email tatiana.kalin@cchmc.org

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Transcriptional regulation of cancer initiation and progression, tumor microenvironment, tumor associated angiogenesis and metastasis. Chemotherapeutic drug development.

Visit the Kalin Lab.

Postdoctoral research fellow: University of Chicago, Chicago, IL.

PhD: Institute of Immunology, Moscow , Russia, 1997.

MD: Moscow Medical University II, Moscow, Russia, 1992.

Balli D, Ren X, Chou FS, Cross E, Zhang Y, Kalinichenko VV, Kalin TV. Foxm1 transcription factor is required for macrophage migration during lung inflammation and tumor formation. Oncogene. 2011 Dec 5. doi: 10.1038/onc.2011.549.

Kalin TV, Ustiyan V, Kalinichenko VV. Multiple faces of FoxM1 transcription factor: Lessons from transgenic mouse models. Cell Cycle. 2011 Feb 1;10(3).

Balli D, Zhang Y, Snyder J, Kalinichenko VV, Kalin TV. Endothelial cell-specific deletion of transcription factor FoxM1 increases urethane-induced lung carcinogenesis. Cancer Res. 2011 Jan 1;71(1):40-50.

Ren X, Zhang Y, Snyder J, Cross ER, Shah TA, Kalin TV, Kalinichenko VV. Forkhead box M1 transcription factor is required for macrophage recruitment during liver repair. Mol Cell Biol. 2010 Nov;30(22):5381-93.

Wang IC, Meliton L, Ren X, Zhang Y, Balli D, Snyder J, Whitsett JA, Kalinichenko VV, Kalin TV. Deletion of Forkhead Box M1 transcription factor from respiratory epithelial cells inhibits pulmonary tumorigenesis. PLoS One. 2009 Aug 12;4(8):e6609.

Kalin TV, Wang IC, Meliton L, Zhang Y, Wert SE, Ren X, Snyder J, Bell SM, Graf L Jr, Whitsett JA, Kalinichenko VV. Forkhead Box m1 transcription factor is required for perinatal lung function. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19330-5.

Kalin TV, Meliton L, Meliton AY, Zhu X, Whitsett JA, Kalinichenko VV. Pulmonary mastocytosis and enhanced lung inflammation in mice heterozygous null for the Foxf1 gene. Am J Respir Cell Mol Biol. 2008 Oct;39(4):390-9.

Wang IC, Meliton L, Tretiakova M, Costa RH, Kalinichenko VV, Kalin TV. Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors. Oncogene. 2008 Jul 10;27(30):4137-49.

Grants

Transcriptional Regulation of Cancer Progression and Metastasis. Principal Investigator. American Cancer Society, Research Scholar Grant. Jul 2013 – Jun 2017. RSG-13-325.

Vladimir V. Kalinichenko, MD, PhD

513-636-4822 vladimir.kalinichenko@cchmc.org

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Vladimir V. Kalinichenko, MD, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4822

Fax 513-636-2423

Email vladimir.kalinichenko@cchmc.org

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Clinical

Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.

Research

MD: Russian State Medical University, Moscow, Russia, 1993.

PhD: Russian State Medical University, Moscow, Russia, 1995.

Fellowship: From the European Soros Foundation, 1995.

Postdoctoral: University of Illinois at Chicago, Center for Molecular Biology, IL, 2000.

Postdoctoral: University of Illinois at Chicago, Department of Molecular Genetics, IL, 2002.

Suhas G. Kallapur, MD Director, Neonatology Continuing Medical Education

is interested in understanding how the fetus copes with and adapts to infectious and inflammatory insults in utero e.g. exposure to chorioamnionitis. Dr. Kallapur’s research focus is to understand the pathogenesis of lung injury and systemic inflammatory responses in fetuses and newborns. His lab uses a sheep model and has begun some work in humans.
Visit the Kallapur Lab.

513-636-3879 suhas.kallapur@cchmc.org

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Suhas G. Kallapur, MD

Director, Neonatology Continuing Medical Education

Global Health Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3879

Fax 513-636-7868

Email suhas.kallapur@cchmc.org

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Clinical

Chorioamnionitis; bronchopulmonary dysplasia; respiratory distress syndrome; fetal immunity

Research

Visit the Kallapur Lab.

MBBS: University of Bombay, India, 1984.

DCH: College of Physicians and Surgeons, Bombay, India, 1986.

MD, Pediatrics: University of Bombay, India, 1986.

Residency: University of Bombay, India, 1984-87.

Residency: Children's Hospital of Michigan, Detroit, MI, 1988-90.

Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1990-1993.

Kemp MW, Kallapur SG, Jobe AH, Newnham JP. Obesity and the developmental origins of health and disease. J Paediatr Child Health. 2011 Jan 18.

Morrow AL, Meinzen-Derr J, Huang P, Schibler KR, Cahill T, Keddache M, Kallapur SG, Newburg DS, Tabangin M, Warner BB, Jiang X. Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants. J Pediatr. 2011 May;158(5):745-51.

Hillman NH, Kallapur SG, Pillow JJ, Nitsos I, Polglase GR, Ikegami M, Jobe AH. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep. Respir Res. 2010 Oct 29;11:151.

Shah TA, Hillman NH, Nitsos I, Polglase GR, Pillow JJ, Newnham JP, Jobe AH, Kallapur SG. Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis. Pediatr Res. 2010 Sep;68(3):210-5.

Shah TA, Hillman NH, Nitsos I, Polglase GR, Pillow JJ, Newnham JP, Jobe AH, Kallapur SG. Pulmonary and Systemic Expression of Monocyte Chemotactic Proteins in Preterm Sheep Fetuses Exposed to LPS Induced Chorioamnionitis. Pediatr Res. 2010 May 28.

Jobe AH, Kallapur SG. Long term consequences of oxygen therapy in the neonatal period. Semin Fetal Neonatal Med. 2010 Aug;15(4):230-5.

Hillman NH, Pillow JJ, Ball MK, Polglase GR, Kallapur SG, Jobe AH. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep. Respir Res. 2009 Dec 15;10:124.

Hillman NH, Kallapur SG, Pillow JJ, Moss TJ, Polglase GR, Nitsos I, Jobe AH. Airway injury from initiating ventilation in preterm sheep. Pediatr Res. 2010 Jan;67(1):60-5.

Jobe AH, Nitsos I, Pillow JJ, Polglase GR, Kallapur SG, Newnham JP. Betamethasone dose and formulation for induced lung maturation in fetal sheep. Am J Obstet Gynecol. 2009 Dec;201(6):611.e1-7.

Kallapur SG, Moss TJ, Auten RL Jr, Nitsos I, Pillow JJ, Kramer BW, Maeda DY, Newnham JP, Ikegami M, Jobe AH. IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung. Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L512-9.

Beena D. Kamath-Rayne, MD, MPH Attending Neonatologist, Neonatology and Pulmonary Biology

does clinical/translational research in preterm birth, fetal maturity and timing of delivery using biomarkers in amniotic fluid transcriptome. She is jointly appointed in Global Health. She is the associate editor for the 2nd Edition of Helping Babies Breathe (HBB), a global curriculum in neonatal resuscitation. She serves on the American Academy of Pediatrics Helping Babies Survive Planning Group. She is collaborating on several research studies of HBB around the world.

513-803-1606 beena.kamath-rayne@cchmc.org

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Beena D. Kamath-Rayne, MD, MPH

Attending Neonatologist, Neonatology and Pulmonary Biology

Global Health Center

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1606

Fax 513-636-0171

Email beena.kamath-rayne@cchmc.org

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Perinatal epidemiology and public health; global health

Biography

Dr. Kamath-Rayne is doing collaborative research with maternal-fetal medicine on preterm birth, fetal maturity, and biomarker discovery in amniotic fluid, with the hopes of developing less invasive tests of fetal maturity. She has received a BIRCWH K12 OMICS K12, and Perinatal Institute Pilot and Feasibility awards to fund this research. She has published on neonatal outcomes after elective Cesarean section, and after documented fetal lung maturity. Her work was required reading for the Maintenance for Certification for the American Board of Obstetrics and Gynecology in 2010.

Dr. Kamath-Rayne is jointly appointed in Global Health and serves on the American Academy of Pediatrics Helping Babies Survive Planning Group. She is the associate editor for the 2nd Edition of Helping Babies Breathe (HBB), a global curriculum in neonatal resuscitation, and contributing editor to Essential Care for Small Babies. She is collaborating on several research studies of HBB around the world. With Dr. Alan Jobe, she has served as a neonatal consultant for MANDATE (Maternal and Neonatal Directed Assessment of Technology), a project funded by the Bill and Melinda Gates Foundation to RTI International to inform the development of technologies to decrease maternal and neonatal mortality worldwide. Finally, she does research on educational outcomes of teaching neonatal resuscitation to pediatric residents.

MD: Georgetown University, Washington, DC, 2000.

Residency: Children's Hospital Colorado/University of Colorado Health Sciences, Denver, CO, 2003.

Fellowship: Children's Hospital Colorado/University of Colorado Health Sciences, Denver, CO, 2008.

MPH: Colorado School of Public Health, Aurora, CO, 2008.

Kamath-Rayne BD, Du Y, Hughes M, Wagner E, Muglia LJ, DeFranco EA, Whitsett JA, Salomonis N, Xu Y. Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity. BMC Med Genomics. 2015;8(1):67.

Seto TL, Tabangin ME, Josyula S, Taylor KK, Vasquez JC, Kamath-Rayne BD. Educational outcomes of Helping Babies Breathe training at a community hospital in Honduras. Perspect Med Educ. 2015;4(5):225-32.

Kamath-Rayne BD, Griffin JB, Moran K, Jones B, Downs A, McClure EM, Goldenberg RL, Rouse D, Jobe AH. Resuscitation and obstetrical care to reduce intrapartum-related neonatal death: A MANDATE study. Matern Child Health J. 2015;12(Suppl 2):S13.

Kamath-Rayne BD, Habli M, Rodriguez Z, Wu M, Gresh J, DeFranco EA. Antenatal exposure to sulindac and risk of necrotizing enterocolitis. Am J Obstet Gynecol. 2015 Jan;212(1):96.e1-7.

Hall ES, Folger AT, Kelly E, Kamath-Rayne BD. Impact of gestational age estimate method on the calculation of preterm birth rates. Matern Child Health J. 2014;18(3):755-62.

Kamath-Rayne BD, DeFranco EA, Marcotte MP. Antenatal steroids for treatment of fetal lung immaturity after 34 weeks of gestation: An evaluation of neonatal outcomes. Obstet Gynecol. 2012;119(5):909-916.

Kamath BD, Marcotte, MP, DeFranco, EA. Neonatal morbidity after documented fetal lung maturity in late preterm and early term infants. Am J Obstet Gynecol. 2011; 204: 518.e1-e8.

Kamath BD, MacGuire ER, McClure EM, Goldenberg RL, Jobe AH. Neonatal mortality from respiratory distress syndrome: a historical review with lessons for low-resource countries. Pediatrics. 2011; 127(6):1139-46.

Kamath BD, Todd JK, Glazner JE, Lezotte D, Lynch AM. Neonatal outcomes after elective Cesarean section. Obstetr Gynecol. 2009; 113(6): 1231-1238. *Required reading for Maintenance of Certification for American Board of Obstetrics and Gynecology, 2010.

Kamath BD, Box TL, Simpson M, Hernández J. Infants born at the threshold of viability in relation to neonatal mortality: Colorado, 1991 to 2003. J Perinatol. 2008; 28(5): 354-360.

Grants

Prediction of Fetal Maturity Using Novel Biomarkers from Cell Free Amniotic Fluid Transcriptome. Principal Investigator. National Institutes of Health OMICS K12. Nov 2014-Oct 2016.

Retention of neonatal resuscitation skills in pediatric residents. Principal Investigator. Perinatal Institute Pilot and Feasibility Grant. Jul 2015-Jun 2017.

Heather C. Kaplan, MD, MSCE Attending Neonatologist, Neonatology and Pulmonary Biology

focuses on understanding variations in evidence-based care practices across hospitals and identifying strategies for increasing the implementation of evidence and other innovations into practice. She recently began a line of investigation aimed at building the evidence base for quality improvement so that QI can be used more effectively as a strategy for improving quality and patient outcomes.

513-803-0478 heather.kaplan@cchmc.org

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Heather C. Kaplan, MD, MSCE

Attending Neonatologist, Neonatology and Pulmonary Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-0478

Fax 513-636-0171

Email heather.kaplan@cchmc.org

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Understanding variations in evidence-based care practices across hospitals; examining strategies for increasing the implementation of evidence into practice in perinatal care; using a systems lens to understand and ultimately change behavior at the individual, group, organizational, and environmental levels of the health care system.

Biography

Heather C. Kaplan, MD, MSCE, is passionate about improving the quality and safety of perinatal care and has a solid foundation in epidemiology and research fundamentals. Through her role in the Ohio Perinatal Quality Collaborative, she gained practical experience in the use of quality improvement methods to reduce preterm births and improve outcomes of preterm newborns in Ohio and has formed collaborative relationships with obstetrical and neonatal care providers across the state.

Additionally she has an understanding care delivery in a complex system requires taking a multidisciplinary, multilevel approach. Her career includes didactic coursework in multidisciplinary theories and methods.

BA: Washington University, St. Louis, MO.

MD: Northwestern University, Chicago, IL.

Residency: Children's National Medical Center, Washington, DC.

Fellowship: The Children's Hospital of Philadelphia, Philadelphia, PA.

MSCE: University of Pennsylvania, Philadelphia, PA.

Kaplan HC, Lannon C, Walsh MC, Donovan EF; Ohio Perinatal Quality Collaborative. Ohio statewide quality-improvement collaborative to reduce late-onset sepsis in preterm infants. Pediatrics. 2011 Mar;127(3):427-35.

Kaplan HC, Lorch SA, Pinto-Martin J, Putt M, Silber JH. Assessment of surfactant use in preterm infants as a marker of neonatal intensive care unit quality. BMC Health Serv Res. 2011 Jan 31;11:22.

Kaplan HC, Brady PW, Dritz MC, Hooper DK, Linam WM, Froehle CM, Margolis P. The influence of context on quality improvement success in health care: a systematic review of the literature. Milbank Q. 2010 Dec;88(4):500-59.

Kaplan, HC, Tabangin ME, McClendon D, Meinzen-Derr J, Margolis PA, Donovan EF. Understanding Variation in Vitamin A Supplementation Among NICUs. Pediatrics. 2010 Aug;126(2):e367-73.

Alan P. Kenny, MD, PhD

studies the molecular mechanisms controlling the earliest stages of respiratory and digestive organ development, including the role of a pool of foregut progenitor cells in the ventral endoderm which are induced by FGF and BMP signals emanating from the cardiogenic mesenchyme.

513-803-2224 alan.kenny@cchmc.org

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Alan P. Kenny, MD, PhD

Academic Affiliations

Instructor, UC Department of Pediatrics

Phone 513-803-2224

Fax 513-636-7868

Email alan.kenny@cchmc.org

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Clinical

Neonatal care; neonatal lung disease; neonatal malformations and anomalies

Research

Lung progenitor development; stem cell differentiation; fetal malformations

Biography

Alan P. Kenny, MD, PhD, focuses his research on elucidating the molecular mechanisms controlling the earliest stages of respiratory and digestive organ development. Available evidence suggests that early lung, liver, and pancreas lineages develop from a pool of foregut progenitor cells in the ventral endoderm. They are induced by FGF and BMP signals emanating from the cardiogenic mesenchyme during early somite stages of development through a mechanism that is highly conserved among vertebrates. Despite significant gains in our understanding of this process, fundamentally important questions remain unanswered. First, how are the common foregut organ progenitors specified? Second, how are FGF and BMP pathways spatiotemporally coordinated such that different organs are induced from the common foregut progenitor? A third and most intriguing question is - what are the endoderm genetic programs activated in response to induction from mesoderm that ultimately direct specific foregut organ development?

These questions remain unanswered mostly due to experimental limitations inherent in mouse embryos, which are small and difficult to dissect at such an early stage. Dr. Kenny uses the experimental advantages of the large, externally developing, abundant Xenopus embryos to address these critical, unresolved issues. Specifically, Dr. Kenny is testing his hypothesis that cardiogenic FGF and BMP signaling of different durations induce different organs. Dr. Kenny’s microarray experiment to identify the endodermal genes induced very early in response to mesodermal signaling. Surprisingly, several negative regulators of BMP signaling were induced early by mesoderm signaling. My preliminary work suggests the hypothesis that BMP inhibitory feedback is a critical component induced during early foregut organ progenitor development. This work should ultimately increase our understanding of normal and abnormal early fetal organ development, lending further insight into foregut malformations such as tracheoesophageal fistula and congenital diaphragmatic hernia. Additionally, this work aims to offer better means to direct human embryonic stem cells toward more foregut organ-specific cell fates for therapeutic purposes.

MD: University of Rochester School of Medicine and Dentistry, Rochester, NY, 2002.

PhD: Biology.

Residency: Golisano Children’s Hospital at Strong, University of Rochester, Rochester, NY, 2002-2005.

Fellowship: Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2005-2008.

Certifications: In Pediatrics, 2007 American Board of Pediatrics; American Board of Pediatrics, Board Eligible in Neonatal-Perinatal Medicine, 2008.

Kenny AP, Crimmins NA, Mackay DJ, Hopkin RJ, Bove KE, Leonis MA. Concurrent course of transient neonatal diabetes with cholestasis and paucity of interlobular bile ducts: a case report. Pediatr Dev Pathol. 2009 Sep-Oct;12(5):417-20.

Li Y, Rankin SA, Sinner D, Kenny AP, Krieg PA, Zorn AM. Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling. Genes Dev. 2008 Nov 1;22(21):3050-63.

Kenny A. Vitamin A for prevention of bronchopulmonary dysplasia. Preemie Press. Local news brief for Good Samaritan Hospital. 2007.

Angerer LM, Kenny AP, Newman LA, Angerer RC. Mutual antagonism of SoxB1 and canonical Wnt signaling in sea urchin embryos. Signal Transduction Wiley Interscience, New York. 2007 7(2), 174-178.

Paul S. Kingma, MD, PhD Neonatal Director, Cincinnati Fetal Center

investigates the role of the innate immune system in neonatal infection. Specific projects currently focus on the role of surfactant protein D in neonatal sepsis and acute respiratory distress syndrome and on neutrophil function in cystic fibrosis patients.

513-636-2995 paul.kingma@cchmc.org

Thomas R. Korfhagen, MD, PhD Attending Pediatrician, Neonatology and Pulmonary Biology

studies the roles and mechanisms whereby surfactant proteins A, B, D, Relm peptides and EGF receptor signaling control lung infections, inflammation and responses to lung injury. Translational studies assessing processes to reduce the extent of lung injury and remodeling in neonates and adults.

513-636-7216 thomas.korfhagen@cchmc.org

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Thomas R. Korfhagen, MD, PhD

Attending Pediatrician, Neonatology and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7216

Fax 513-636-7868

Email thomas.korfhagen@cchmc.org

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Clinical

Care of high-risk infants; pediatric patients with complex, long term medical problems

Research

Roles and mechanisms whereby surfactant proteins A, B, D, Relm peptides and EGF-R signaling control lung infections, inflammation and responses to lung injury. Translational studies assessing processes to reduce the extent of lung injury and remodeling in neonates and adults.

BA: University of Cincinnati, Cincinnati, OH, 1972.

PhD: University of Cincinnati, Cincinnati, OH, 1976.

MD: University of Cincinnati, Cincinnati, OH, 1981.

Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1981-1984.

Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH 1984-1987 (Peter Dignan, Director).

Certifications: National Board of Medical Examiners, 7/1982; American Board of Pediatrics, 5/1986; American Board of Medical Genetics, 6/1987.

Hassett DJ, Korfhagen TR, Irvin RT, Schurr MJ, Sauer K, Lau GW, Sutton MD, Yu H, Hoiby N. Pseudomonas aeruginosa biofilm infections in cystic fibrosis: insights into pathogenic processes and treatment strategies. Expert Opin Ther Targets. 2010 Feb;14(2):117-30. Review.

Le Cras TD, Korfhagen TR, Davidson C, Schmidt S, Fenchel M, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Pathol. 2010 Feb;176(2):679-86.

Chen G, Korfhagen TR, Xu Y, Kitzmiller J, Wert SE, Maeda Y, Gregorieff A, Clevers H, Whitsett JA. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J Clin Invest. 2009 Oct;119(10):2914-24.

Deshmukh HS, McLachlan A, Atkinson JJ, Hardie WD, Korfhagen TR, Dietsch M, Liu Y, Di PY, Wesselkamper SC, Borchers MT, Leikauf GD. Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production. Am J Respir Crit Care Med. 2009 Nov 1;180(9):834-45.

Glasser SW, Witt TL, Senft AP, Baatz JE, Folger D, Maxfield MD, Akinbi HT, Newton DA, Prows DR, Korfhagen TR. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L64-72.

Korfhagen TR, Le Cras TD, Davidson CR, Schmidt SM, Ikegami M, Whitsett JA, Hardie WD. Rapamycin prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2009 Nov;41(5):562-72.

Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Khurana Hershey GK, Korfhagen TR, Hardie WD, Whitsett JA, Le Cras TD. Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol. 2009 Oct;41(4):415-25.

Hardie WD, Davidson C, Ikegami M, Leikauf GD, Le Cras TD, Prestridge A, Whitsett JA, Korfhagen TR. EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-alpha-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1217-25.

Deshmukh HS, Shaver C, Case LM, Dietsch M, Wesselkamper SC, Hardie WD, Korfhagen TR, Corradi M, Nadel JA, Borchers MT, Leikauf GD. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. Am J Respir Cell Mol Biol. 2008 Apr;38(4):446-54.

Timothy D. LeCras, PhD Associate Director of Admissions, Medical Scientist Training Program

studies the regulation of vascular and alveolar morphogenesis in the developing lung, as well as mechanisms to stimulate lung regeneration/growth in children and adults. A major focus is the causes and pathways mediating lung remodeling in premature newborns (BPD), pulmonary hypertension (PH), and asthma and to identify new therapeutic targets to treat and prevent these chronic lung diseases.

Visit the LeCras Lab.

513-636-8151 tim.lecras@cchmc.org

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Timothy D. LeCras, PhD

Associate Director of Admissions, Medical Scientist Training Program

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-8151

Fax 513-636-7868

Email tim.lecras@cchmc.org

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Lung development; bronchopulmonary dysplasia; pulmonary hypertension; asthma; pulmonary fibrosis

Biography

Timothy LeCras, PhD, investigates the causes of chronic lung diseases, including pulmonary hypertension, bronchopulmonary dysplasia, pulmonary fibrosis, and asthma. The goal of his laboratory is to use this knowledge to identify therapeutic targets and preventative measures. Our efforts are aided by very productive collaborations with other groups at Cincinnati Children's as well as other groups in the U.S.

Postdoctoral fellow: University of Virginia, Charlottesville, VA, 1993-1996.

PhD: University of Cambridge, UK, 1988-1992.

BSc: Biochemistry, Brunel University, London, UK, 1983-1987.

Acciani TH, Brandt EB, Khurana Hershey GK, Le Cras TD. (2013) Diesel Exhaust Particle Exposure Exacerbates Allergic Asthma in Young Mice. Clin Exp Allergy. 2013 Dec;43(12):1406-18. *Selected for Editors Choice in December issue 2013 Clin Exp Allergy.

Mushaben EM, Brandt EB, Hershey GKK, Le Cras TD. Differential Effects of Rapamycin and Dexamethasone in Mouse Models of Established Allergic Asthma. PLoS ONE. 2013;8(1):e54426.

Mushaben EM, Khurana Hershey GK, Pauciulo MW, Nichols WC, Le Cras TD. Chronic allergic inflammation causes vascular remodeling and pulmonary hypertension in BMPR2 hypomorph and wild-type mice. PLoS ONE. 2012:7(3):e32468.

Kramer EL, Hardie WD, Mushaben E, Acciani T, Pastura P, Korfhagen T, Khurana Hershey G, Whitsett JA, Le Cras TD. Rapamycin Decreases Airway Remodeling and Hyperreactivity in a Transgenic Model of Noninflammatory Lung Disease. J Appl Physiol. 2011 Dec;111:1760-7.

Mushaben EM, Kramer EL, Brandt EB, Khurana Hershey G, Le Cras TD. Rapamycin Attenuates Airway Hyperreactivity, IgE, T cells and Mediators of Allergic Asthma. J Immunol. 2011 Dec 1;187(11):5756-63.

Le Cras TD, Acciani TH, Mushaben EM, Kramer EL, Pastura PA, Hardie WD, Korfhagen TR, Sivaprasad U, Ericksen M, Gibson A, Holtzman MJ, Whitsett JA, Khurana Hershey GK. Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L414-21.

Le Cras TD, Korfhagen TR, Davidson C, Schmidt S, Fenchel M, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K prevents transforming growth factor-alpha induced pulmonary fibrosis. Am J Path. 2010 Feb;176(2):679-86.

Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Khurana Hershey GK, Korfhagen TR, Hardie WD, Whitsett JA, Le Cras TD. Early growth response-1 suppresses Epidermal Growth Factor Receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol. 2009 Oct;41(4):415-25.

Kramer EL, Deutsch GH, Sartor M, Ikegami M, Hardie WD, Korfhagen TR, Le Cras TD. Perinatal induction of TGF-{alpha} disrupts the saccular phase of lung morphogenesis and causes remodeling: Microarray analysis. Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L314-27.

Le Cras TD, Hardie WD, Deutsch GH, Albertine KH, Ikegami M, Whitsett JA, Korfhagen TR. Transient induction of TGF-alpha disrupts lung morphogenesis, causing pulmonary disease in adulthood. Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L718-729. *Published along with an editorial: D. Massaro and G. DeCarlo Massaro. (2004) Critical period for alveologenesis and early determinants of adult pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 287: L715-L717.

Kristin R. Melton, MD Associate Program Director, Neonatal-Perinatal Medicine Fellowship

is interested in early craniofacial development and focuses on the tissue interactions that direct the formation, migration and differentiation of neural crest cells. The Melton Lab focuses on understanding the influence of the endothelium and the cranial mesoderm on neural crest development.

513-803-0022

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Kristin R. Melton, MD

Associate Program Director, Neonatal-Perinatal Medicine Fellowship

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-0022

Fax 513-636-7868

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Clinical

Congenital malformations

Research

Craniofacial malformations; somitogenesis

Biography

Craniofacial defects are an important cause of morbidity for children worldwide, with craniofacial defects making up one third of all congenital anomalies and occurring in association with over 100 different genetic syndromes. Cranial neural crest cells are multipotent, migratory cells that form most of the bone, cartilage, connective tissue and peripheral nervous system of the head and face. Craniofacial defects are largely attributed to abnormalities in the formation, migration or differentiation of the neural crest. The cranial neural crest is responsive to the tissues that surround it, however, so craniofacial defects may result from a primary defect in neural crest cells, or from a defect in the tissues that signal to neural crest.

Kristin Melton, MD, has an interest in studying the tissues that signal to the neural crest, such as the endothelium and cranial mesoderm, and the signaling pathways utilized by these tissues. Using embryo culture techniques, cell culture and transgenic mouse models, Dr. Melton is investigating the interaction between the endothelium and the neural crest. Microarray has also been used to identify a number of mesoderm-specific genes that may play key roles in craniofacial development.

Dr. Melton is a practicing neonatologist and attends at the RCNIC in Cincinnati Children’s Hospital Medical Center. Her clinical interests include newborns with complex congenital anomalies and genetic defects, as well as a focus on family-centered care.

BA: Washington University, St. Louis, MO, 1991.

MD: University of Nebraska, Omaha, NE, 1995.

Residency: Children's Mercy Hospital, Kansas City, MO, 1998.

Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2001.

Gibb S, Zagorska A, Melton K, Tenin G, Vacca I, Trainor P, Maroto M, Dale JK. Interfering with Wnt signalling alters the periodicity of the segmentation clock. Dev Biol. 2009 Jun 1;330(1):21-31.

Nesslein LL, Melton KR, Ikegami M, Na CL, Wert SE, Rice WR, Whitsett JA, Weaver TE. Partial SP-B deficiency perturbs lung function and causes air space abnormalities. Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1154-61.

Melton KR, Nesslein LL, Ikegami M, Tichelaar JW, Clark JC, Whitsett JA, Weaver TE. SP-B deficiency causes respiratory failure in adult mice. Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L543-9.

Melton K, Akinbi HT. Neonatal jaundice. Strategies to reduce bilirubin-induced complications. Postgrad Med. 1999 Nov;106(6):167-8, 171-4, 177-8.

Stephanie L. Merhar, MD, MS Attending Neonatologist, Neonatology and Pulmonary Biology

is interested in optimizing neuroimaging in preterm and term infants at risk for brain injury, neonatal seizure treatment and neurodevelopmental outcomes of infants in the NICU.

513-803-5180 stephanie.merhar@cchmc.org

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Stephanie L. Merhar, MD, MS

Attending Neonatologist, Neonatology and Pulmonary Biology

Research Director, NICU Follow Up Clinic
Follow Up Principal Investigator, Cincinnati site, NICHD Neonatal Research Network

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-5180

Email stephanie.merhar@cchmc.org

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Biography

Stephanie L. Merhar, MD, MS, is a neonatologist with a research focus in the field of neuroimaging, developing ways to use advanced imaging techniques to predict and improve the outcomes of term and preterm babies with brain injury.

MD: University of Pennsylvania, Philadelphia, PA, 2005.

Residency: Pediatrics, Cincinnati Children's Hospital Medical Center, 2005-2008.

Fellowship: Neonatology, Cincinnati Children's Hospital Medical Center, 2008-2011.

Certification: Pediatrics, 2008.

Merhar S. Biomarkers in neonatal posthemorrhagic hydrocephalus. Neonatology. 2011 Jul;101(1):1-7.

Merhar SL, Schibler KR, Sherwin CM, Meinzen-Derr J, Shi J, Balmakund T, Vinks AA. Pharmacokinetics of levetiracetam in neonates with seizures. J Pediatrics. 2011 Jul;159(1):152-154.

Merhar SL, Manning-Courtney P. Two boys with 47 XXY and autism. J Autism Devl Disord. 2007 May;37(5):840-6.

Merhar SL, Gilbert DL. Clinical (video) findings and cerebrospinal fluid neurotransmitters in 2 children with severe chronic bilirubin encephalopathy, including a former preterm infant without marked hyperbilirubinemia. Pediatrics. 2005 Nov;116(5):1226-30.

Levy SE, Mandell DS, Merhar SL, Ittenbach RF, Pinto-Martin JA. Use of complementary and alternative medicine among children recently diagnosed with autistic spectrum disorder. J Dev Behav Ped. 2003 Dec;24(6):418-423.

Vivek Narendran, MD, MRCP, MBA Medical Director, University of Cincinnati Medical Center NICU

is interested in innate immunity of the skin with a particular focus on epidermal biomarkers and antimicrobial peptides on the skin surface.

513-803-0961 vivek.narendran@cchmc.org

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Vivek Narendran, MD, MRCP, MBA

Medical Director, University of Cincinnati Medical Center NICU

Medical Director, Cincinnati Perinatal Outreach Project

Director, Neonatal Intensive Care Unit and Newborn Services, Christ Hospital

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-0961

Fax 513-803-0969

Email vivek.narendran@cchmc.org

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Clinical

Non-invasive ventilation of the preterm infant; business case for quality improvements

Research

Interested in innate immunity of the skin with a particular focus on epidermal biomarkers and antimicrobial peptides on the skin surface

MBBS: Bangalore Medical College, Bangalore, India, 1985.

MD/DNB: JN Medical College, Belgaum, India, 1990.

Fellowship: Neonatology, Westmead Hospital, Sydney, Australia, 1992-94.

Residency: Pediatrics, Leicester Royal Infirmary, Leicester, United Kingdom, 1994-1996.

Residency: Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1997-1998.

Fellowship: Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1996, 1998-2000.

Credentials: Pediatrics, 1998; Pediatrics, Royal College of Physicians (MRCP), United Kingdom, 1996; Neonatal-Perinatal Medicine 2001 & 2008.

Binder S, Hill K, Meinzen-Derr J, Greenberg JM, Narendran V. Increasing VLBW Deliveries at Subspecialty Perinatal Centers via Perinatal Outreach. Pediatrics. 2011 Feb 14.

Narendran V, Visscher MO, Abril I, Hendrix SW, Hoath SB. Biomarkers of epidermal innate immunity in premature and full-term infants. Pediatr Res. 2010 Apr;67(4):382-6.

Walker VP, Akinbi HT, Meinzen-Derr J, Narendran V, Visscher M, Hoath SB. Host defense proteins on the surface of neonatal skin: implications for innate immunity. J Pediatr. 2008 Jun;152(6):777-81.

Sampath V, Narendran V, Donovan EF, Stanek J, Schleiss MR. Nonimmune hydrops fetalis and fulminant fatal disease due to congenital cytomegalovirus infection in a premature infant. J Perinatol. 2005 Sep;25(9):608-11.

Visscher MO, Narendran V, Pickens WL, LaRuffa AA, Meinzen-Derr J, Allen K, Hoath SB. Vernix caseosa in neonatal adaptation. J Perinatol. 2005 Jul;25(7):440-6. Review.

Akinbi HT, Narendran V, Pass AK, Markart P, Hoath SB. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. 2004 Dec;191(6):2090-6.

Narendran V, Donovan EF, Hoath SB, Akinbi HT, Steichen JJ, Jobe AH. Early bubble CPAP and outcomes in ELBW preterm infants. J Perinatol. 2003 Apr-May;23(3):195-9.

Hoath SB, Narendran V. Adhesives and emollients in the preterm infant. Semin Neonatol. 2000 Nov;5(4):289-96. Review.

Narendran V, Wickett RR, Pickens WL, Hoath SB. Interaction between pulmonary surfactant and vernix: a potential mechanism for induction of amniotic fluid turbidity. Pediatr Res. 2000 Jul;48(1):120-4.

Amy T. Nathan, MD Medical Director, Neonatology and Pulmonary Biology

focuses on antecedent factors leading to necrotizing enterocolitis and is interested in applying quality improvement methods to reduce the incidence of this major morbidity in preterm infants.

513-803-0909 amy.nathan@cchmc.org

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Amy T. Nathan, MD

Medical Director, Neonatology and Pulmonary Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-0909

Email amy.nathan@cchmc.org

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Clinical

Necrotizing enterocolitis; quality improvement; neonatal immune responses; family-centered care

Research

Immune modulation of lung injury and inflammation

Biography

Innate immune responses at the epithelial boundaries in preterm infants (lung, intestine) can be protective, but inflammatory responses may also cause significant damage. Necrotizing enterocolitis is a devastating, multi-factorial disease marked by intense inflammation, which may be related to changes in the intestinal microbiome combined with compromised perfusion. Dr. Nathan focuses on antecedent factors leading to necrotizing enterocolitis and is interested in applying quality improvement methods to reduce the incidence of this major morbidity in preterm infants.

MD: Yale University School of Medicine, New Haven, CT, 1998.

Residency: University of North Carolina, Chapel Hill, NC, 1998-2002.

Fellowship: University of North Carolina, Chapel Hill, NC, 2002-2005.

Certification: Pediatrics 2001; Neonatology, 2008.

Wills-Karp M, Nathan A, Page K, Karp CL. New insights into innate immune mechanisms underlying allergenicity. Mucosal Immunol. 2010 Mar;3(2):104-10.

Nathan AT, Peterson EA, Chakir J, Wills-Karp M. Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. J Allergy Clin Immunol. 2009 Mar;123(3):612-8.

Chavez-Valdez R, Ahlawat R, Wills-Karp M, Nathan AT, Ezell T, and Gauda EB. Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants. J Peds. Aug 5 2010.

Wexelblatt, SL, Greenberg, JM, and Nathan AT. Regional care model enables rapid response to adverse drug events. J Perintatol. 2010 30: 300-2.

Chavez-Valdez R, Wills-Karp M, Ahlawat R, Cristofalo EA, Nathan AT, and Gauda EB. Caffeine modulates TNF- production by cord blood monocytes; the role of adenosine receptors. Ped Research. 2009 65(2):203-8.

Wendel KR, Nathan AT. Inhaled nitric oxide. Newborn and Infant Nursing Reviews. 2006 6(2):100-105.

Nehal A. Parikh, DO, MS Attending Neonatologist, Perinatal Institute

investigates the etiology and development of perinatal brain injury/delayed brain development in high-risk newborns and early identification of prognostic biomarkers of neurodevelopmental disabilities. The goal of his research is to provide insight into abnormal brain development/injury and prevent disabilities through early risk stratification and rigorous clinical trials of neuroprotective interventions.

513-636-7584 nehal.parikh@cchmc.org

Nehal A. Parikh, DO, MS

Attending Neonatologist, Perinatal Institute

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7584

Email nehal.parikh@cchmc.org

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Clinical

Evidence-based and family-centered care of very premature infants and term infants with asphyxia/neonatal encephalopathy; critically-ill newborns

Research

Early diagnosis of perinatal brain injury/delayed brain development; prediction and prevention of neurodevelopmental disabilities

Biography

Dr. Nehal Parikh’s singular goal is to prevent neurodevelopmental disabilities. Following rigorous training in translational research and clinical trials, he embarked on studies of etiology, prediction and prevention of neurodevelopmental disabilities in high-risk newborns. He has led or co-led several cohort studies of advanced brain MRI in very preterm infants, clinical trials of neuroprotective therapies in high-risk newborns, and the development of the NICHD NRN Extremely Preterm Birth Outcomes prognostic calculator and website. Increased survival of extremely preterm infants has contributed to a higher prevalence of survivors with motor, cognitive, and behavioral/psychiatric abnormalities. Accurate diagnosis of these abnormalities takes 2 to 3 years. These early years are when the brain is most active in building its wiring system and optimally receptive to change and healing. Thus, when the diagnosis is delayed by up to 3 years, we are losing precious time. Newer approaches to diagnosis, prediction and prevention of developmental disabilities are urgently needed to improve the long-term quality of life of high-risk newborns.

The Parikh lab employs advanced brain MRI tools such as volumetric, diffusion, and functional MRI for early identification of biomarkers of brain injury/delayed development that are predictive of disabilities in individual high-risk neonates/infants. The lab’s current focus is to understand the nature of the commonly encountered diffuse white matter abnormalities and to develop early prognostic models of motor, cognitive, and behavioral abnormalities in a geographic cohort of 500 very preterm infants. This important step will facilitate risk stratification, soon after birth, to design clinical trials of targeted neuroprotective interventions during the critical window of the first 3 years after birth when brain plasticity is at its peak.

DO: NY College of Osteopathic Medicine of NY Institute of Technology, Long Island, NY, 1996.

Residency: Pediatrics, Winthrop University Hospital of SUNY Stony Brook, Long Island, NY, 1999.

Fellowship: Neonatology, Thomas Jefferson University of Jefferson Medical College, Philadelphia, PA, 2002.

MS: Translational/Clinical Research, University of Texas Medical School at Houston, Houston, TX, 2007.

Certification: Pediatrics, 1996.

Certification: Neonatology, 2003, 2010.

Parikh, NA. Advanced Neuroimaging and its Role in Predicting Neurodevelopmental Outcomes in Very Preterm Infants. Seminars in Perinatology. 2016.

He L, Parikh NA. Brain Functional Network Connectivity Development in Very Preterm Infants: The First Six Months. Early Human Development. 2016;98:29-35.

Pogribna U, Burson K, Lasky RE, Narayana PA, Evans PW, Parikh NA. Role of Diffusion Tensor Imaging (DTI) as an Independent Predictor of Cognitive and Language Development in Extremely Preterm Infants. Am J of Neuroradiol. 2014;35(4):790-796.

Kaur S, Powell S, He L, Pierson C, Parikh NA. Reliability and repeatability of quantitative tractography methods for mapping structural white matter connectivity in preterm and term infants at term-equivalent age. PLoS One. 2014;9(1):e85807.

Parikh NA, He L, Bonfante-Mejia E, Hochhauser L, Evans P, Burson K, Kaur S. Automatically Quantified Diffuse Excessive High Signal Intensity on MRI Predicts Cognitive Development in Preterm Infants. Pediatr Neurol. 2013;49(6):424-30.

Parikh NA, Lasky RE, Kennedy KA, McDavid G, Tyson JE. Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants. PLoS ONE. 2013;8(5):e62804.

Parikh NA, Kennedy KA, Lasky RE, McDavid G, Tyson JE. Pilot Randomized Trial of Hydrocortisone in Ventilator-Dependent Extremely Preterm Infants: Effects on Regional Brain Volumes. J Pediatr. 2012;162(4):685-690.

Yu X, Zhang Y, Lasky RE, Datta S, Parikh NA, Narayana PA. Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns. PLoS One. 2010;5(11):e13874.

Tyson JE, Parikh NA, Langer J, Green C, Higgins R, for the NICHD Neonatal Research Network. Intensive Care for Extreme Prematurity – Moving Beyond Gestational Age. N Engl J Med. 2008;358(16):1672-81.

Parikh NA, Lasky RE, Kennedy KA, Moya FR, Hochhauser L, Romo S, Tyson JE. Postnatal Dexamethasone Therapy and Cerebral Tissue Volumes in Extremely Low Birth Weight Infants. Pediatrics. 2007;119(2):265-272.

Grants

A New Model to Identify Preterm Neonates at High-Risk for Cognitive Deficits. Principal Investigator. National Institutes of Health / National Institute of Neurological Disorders and Stroke. Apr 2016-Jan 2021.

Early Prediction of Cerebral Palsy in Premature Infants using Advanced MRI Biomarkers. Principal Investigator. National Institutes of Health/ National Institute of Neurological Disorders and Stroke. Oct 2016-Sep 2021.

Anne Karina T. Perl, MS, PhD

studies molecular mechanisms underlying normal lung formation and lung repair processes in the preterm and postnatal lung. Data from our laboratory supports the hypothesis of the existence of distinct subsets of endodermaly derived progenitor cells during lung development. Our long-term goal is to understand the characteristics and the fate of these lung progenitors for prevention and therapy of lung disease.
Visit the Perl Lab.

513-636-6084 anne.perl@cchmc.org

High Res

Anne Karina T. Perl, MS, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-6084

Fax 513-636-7868

Email anne.perl@cchmc.org

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Clinical

Lung development and lung regeneration

Research

Visit the Perl Lab.

PhD: University of Vienna, Austria, 1998.

Chen L, Acciani T, Le Cras T, Lutzko C, Perl AK. Dynamic Regulation of Platelet-Derived Growth Factor Receptor α Expression in Alveolar fibroblasts During Realveolarization. Am J Respir Cell Mol Biol. May 31, 2012.

Rawlins EL, Perl AK. The a"MAZE"ing world of lung-specific transgenic mice. Am J Respir Cell Mol Biol. 2012 Mar;46(3):269-82.

Perl AK, Riethmacher D, Whitsett JA. Conditional depletion of airway progenitor cells induces peribronchiolar fibrosis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):511-21.

Perl AK, Gale E. FGF signaling is required for myofibroblast differentiation during alveolar regeneration. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L299-308.

Lin S, Perl AK, Shannon JM. Erm/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. J Biol Chem. 2006 Jun 16;281(24):16716-26.

Martis PC, Whitsett JA, Xu Y, Perl AK, Wan H, Ikegami M. C/EBPalpha is required for lung maturation at birth. Development. 2006 Mar;133(6):1155-64.

Perl AK, Wert SE, Loudy DE, Shan Z, Blair PA, Whitsett JA. Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli. Am J Respir Cell Mol Biol. 2005 Nov;33(5):455-62.

Perl AK, Kist R, Shan Z, Scherer G, Whitsett JA. Normal lung development and function after Sox9 inactivation in the respiratory epithelium. Genesis. 2005 Jan;41(1):23-32.

Miller LA, Wert SE, Clark JC, Xu Y, Perl AK, Whitsett JA. Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung. Dev Dyn. 2004 Sep;231(1):57-71.

Hokuto I, Ikegami M, Yoshida M, Takeda K, Akira S, Perl AK, Hull WM, Wert SE, Whitsett JA. Stat-3 is required for pulmonary homeostasis during hyperoxia. J Clin Invest. 2004 Jan;113(1):28-37.

Grants

Airway Progenitor Cell Proliferation and Differentiation During Lung Repair. Co-investigator. National Institutes of Health/National Heart, Lung and Blood Institute. Dec 2011-Nov 2016. U01 HL110964.

John H. Reuter, MD, PhD Attending Neonatologist, Neonatology and Pulmonary Biology

is active in the administration of a 4000 delivery/year community level II service. His academic interests include breast milk and nutrition in the preterm infant.

513-862-2748 john.reuter@cchmc.org

Ward R. Rice, MD, PhD Medical Director, Newborn Services, St. Elizabeth Medical Center

studies the molecular and cellular mechanisms that regulate processing of surfactant protein C, a protein that is critical for lung function.

513-636-3149 ward.rice@cchmc.org

High Res

Ward R. Rice, MD, PhD

Medical Director, Newborn Services, St. Elizabeth Medical Center

Director, Neonatology Fellowship Training Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3149

Fax 513-636-7868

Email ward.rice@cchmc.org

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Clinical

Hypotension in ELBW infants; EMR

Research

Processing of surfactant protein C

Biography

Ward R. Rice, MD, PhD, is the director of the Neonatology Fellowship Training Program and director of Newborn Services, St. Elizabeth Medical Center.

Dr. Rice received MD and PhD degrees from the University of Chicago and has been on the faculty since 1983. He has been the director of the Neonatology Fellowship Training Program since 1990. During this time, he has supervised the clinical training of more than 100 fellows who currently hold academic appointments across the United States and around the world.

His past NIH supported research accomplishments included identification of novel G-protein coupled receptors on alveolar type II cells and studies of the interaction of the opportunistic pathogen P carinii with alveolar type II cells. He currently works in collaboration with Dr. Timothy Weaver to study biosynthesis of surfactant protein C.

PhD: University of Chicago, Chicago, Illinois, 1972-76.

PhD: Biochemistry, Thesis Advisor: T.L. Steck, MD, Thesis: "Pyruvate Flux Across The Isolated Human Erythrocyte Membrane."

MD: University of Chicago, Chicago, Illinois, 1972-78.

Internship: Duke University Medical Center, Durham, North Carolina, 1978-79.

Residency: Duke University Medical Center, Durham, North Carolina, 1979-81.

Fellowship Neonatology: University of Cincinnati College of Medicine, Children's Hospital Medical Center, 1981-83.

Certification: Pediatrics, 1983; Sub-board Neonatal-Perinatal Medicine, 1983.

Conkright JJ, Apsley KS, Martin EP, Ridsdale R, Rice WR, Na CL, Yang B, Weaver TE. Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C. Am J Respir Cell Mol Biol. 2010 Feb;42(2):181-9.

Nesslein LL, Melton KR, Ikegami M, Na CL, Wert SE, Rice WR, Whitsett JA, Weaver TE. Partial SP-B deficiency perturbs lung function and causes air space abnormalities. Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1154-61.

Rice WR, Conkright JJ, Na CL, Ikegami M, Shannon JM, Weaver TE. Maintenance of the mouse type II cell phenotype in vitro. Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L256-64.

Huffman Reed JA, Rice WR, Zsengellér ZK, Wert SE, Dranoff G, Whitsett JA. GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice. Am J Physiol. 1997 Oct;273(4 Pt 1):L715-25.

Rice W, Shannon JM, Burton F, Fiedeldey D. Expression of a brain-type cannabinoid receptor (CB1) in alveolar Type II cells in the lung: regulation by hydrocortisone. Eur J Pharmacol. 1997 May 30;327(2-3):227-32.

Linke MJ, Burton FM, Fiedeldey DT, Rice WR. Surfactant phospholipid secretion from rat alveolar type II cells: possible role of PKC isozymes. Am J Physiol. 1997 Feb;272(2 Pt 1):L171-7.

Chroneos ZC, Abdolrasulnia R, Whitsett JA, Rice WR, Shepherd VL. Purification of a cell-surface receptor for surfactant protein A. J Biol Chem. 1996 Jul 5;271(27):16375-83.

Haas M, Rice WR. Respiratory distress syndrome for the practicing pediatrician. Pediatr Ann. 1995 Nov;24(11):572-6, 579-80. Review.

Rice WR, Burton FM, Fiedeldey DT. Cloning and expression of the alveolar type II cell P2u-purinergic receptor. Am J Respir Cell Mol Biol. 1995 Jan;12(1):27-32.

Rice WR, Singleton FM, Linke MJ, Walzer PD. Regulation of surfactant phosphatidylcholine secretion from alveolar type II cells during Pneumocystis carinii pneumonia in the rat. JClin Invest. 1993 Dec;92(6):2778-82.

Kurt R. Schibler, MD Attending Neonatologist, Neonatology and Pulmonary Biology

is the principal investigator for the NICHD Neonatal Research Network at Cincinnati Children’s and is also involved in thematic collaborative research investigating the immune mechanisms underlying morbidity and mortality associated with preterm birth. He aims to identify infants at high risk for developing necrotizing enterocolitis and late onset infection and to devise strategies to prevent and to treat these complications.

513-636-3972 kurt.schibler@cchmc.org

High Res

Kurt R. Schibler, MD

Attending Neonatologist, Neonatology and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3972

Fax 513-636-7868

Email kurt.schibler@cchmc.org

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Clinical

Clinical trials; neonatal immune development

Research

Immune mechanisms underlying morbidity and mortality associated with preterm birth; necrotizing enterocolitis; complications of prematurity

MD: University of Cincinnati, Cincinnati, Ohio, 1984.

Residency: Pediatrics, Indiana University, Indianapolis, Indiana, 1990.

Fellowship: Neonatology, University of Utah, Salt Lake City, Utah, 1993.

Certification: Pediatrics 1990; Neonatal-Perinatal Medicine 1993, renewed 1999 and 2007.