Pulmonary Biology

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 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 Co-Director

Timothy E. Weaver, MS, PhD Co-Director, Division of Pulmonary Biology

focuses on the identification of cytoprotective pathways that mediate adaptation to genetic and environmental stresses in the pulmonary epithelium. These molecular pathways play a critical role in preventing or slowing the progression of chronic lung disease and may provide novel targets for therapeutic intervention.
Visit the Weaver Lab.

513-636-7223 tim.weaver@cchmc.org

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Timothy E. Weaver, MS, PhD

Co-Director, Division of Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7223

Fax 513-636-7868

Email tim.weaver@cchmc.org

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Lung development; chaperone biology and diseases of protein misfolding; pulmonary fibrosis; asthma; respiratory distress syndrome; acute and chronic lung disease

Visit the Weaver Lab.

Biography

Dr. Weaver has a long-standing interest in lung development and disease. His early work with Dr. Whitsett uncovered the function of surfactant proteins SP-B and SP-C, a discovery that has profoundly influenced the treatment of respiratory distress syndrome and survival of pre-term infants worldwide. His current research is focused to the molecular pathways (ER stress and autophagy) that link mutations in the SFTPC gene (encoding surfactant protein C) to development of interstitial lung disease (ILD) in both children and adults. His work has been continuously funded by the National Institutes of Health since 1986, including a MERIT (R37) award from the National Heart, Lung and Blood Institute (2001-2011).

Dr. Weaver has trained 14 graduate students in the past 15 years and is the past director of the Molecular and Developmental Biology Graduate Program. During the same period of time he has trained 11 postdoctoral fellows, eight of whom are current faculty members at institutions in the US, Germany, France, Japan and UK.

BS: Biology, Bob Jones University, Greenville, SC, 1975.

MS: Embryology, Hahnemann Medical College, Philadelphia, PA, 1979.

PhD: Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 1983.

Postdoc: Molecular Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 1986.

Hahn DR, Na CL, Weaver TE. Reserve autophagic capacity in alveolar epithelia provides a replicative niche for influenza A virus. Am J Respir Cell Mol Biol. 2014 Sep;51(3):400-12.

Fritz JM, Dong M, Apsley KS, Martin EP, Na CL, Sitaraman S, Weaver TE. Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects. Mol Biol Cell. 2014 Feb; 25(4):431-40.

Ridsdale R, Na CL, Xu Y, Greis KD, Weaver T. Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. PLoS One. 2011 26;6(1):e16482.

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.

Dong M, Bridges JP, Apsley K, Xu Y, Weaver TE. ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C. Mol Biol Cell. 2008 Jun;19(6):2620-30.

Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M, Lang G, Fink L, Bohle RM, Seeger W, Weaver TE, Guenther A. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):838-46.

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.

Johansson H, Nordling K, Weaver TE, Johansson J. The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-val transmembrane segment. J Biol Chem. 2006 Jul 28;281(30):21032-9.

Bridges JP, Xu Y, Na CL, Wong HR, Weaver TE. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. J Cell Biol. 2006 Jan 30;172(3): 395-407.

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.

Grants

Stard7, A Novel Inhibitor Of Allergic Lung Disease. Principal Investigator. National Institutes of Health. Dec 2013-Nov 2017. R01-HL122130.

Faculty

Shawn K. Ahlfeld, MD

investigates the effects of neonatal lung injury on alveolar repair and development. Using developmentally-relevant genetic and physiologic approaches, he is identifying the role of interstitial fibroblasts in mechanisms behind alveolar simplification characteristic of bronchopulmonary dysplasia, with the long-term goal of developing novel therapies that promote normal alveolar lung development and function.

513-803-7723 shawn.ahlfeld@cchmc.org

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Shawn K. Ahlfeld, MD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-7723

Email shawn.ahlfeld@cchmc.org

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Clinical

Neonatal-perinatal medicine; bronchopulmonary dysplasia

Research

Neonatal lung injury, development, and repair; neonatal lung mesenchymal development; biomarkers of neonatal lung injury; animal models of bronchopulmonary dysplasia

Biography

As a neonatal fellow and junior faculty, Dr. Ahlfeld has evaluated the role of matricellular proteins in saccular and early alveolar lung development. He and his team has determined that hyperoxia exposure resulted in the mis-expression of the Transforming Growth Factor Beta (TGFβ)-responsive extracellular matrix protein, periostin, during critical periods of saccular-alveolar lung development. Periostin proved to be a novel marker for both normal myofibroblastic activity during alveolarization and abnormal myofibroblastic persistence during late fibrotic stages of lung injury.

Under a scholar grant through the Prematurity and Respiratory Outcomes Program (PROP), they have demonstrated, for the first time, that plasma periostin levels in extremely premature infants during the first weeks of age correlate with the development and severity of BPD. Their investigations into TGFβ superfamily signaling during saccular and alveolar lung development, as well as its role in BPD pathogenesis, are ongoing.

Contrary to the prevailing notion of up-regulation, TGFβ extracellular signaling ligands, intracellular signaling messengers, and down-stream signaling targets are all down-regulated during early hyperoxic lung injury. They have determined that TGFβ down-regulation coincides with a period of saccular-alveolar lung development that is critical for development of distal lung complexity and function. The down-regulation of TGFβ signaling during this critical window of lung development occurs well before the up-regulation of TGFβ signaling associated with chronic hyperoxic lung injury that they and others have described.

Additionally, his team has identified that a second matricellular protein, TGFβ-induced protein (TGFBI), is a novel extracellular matrix protein mis-expressed by neonatal hyperoxia and vital for normal alveolar development.

Their findings have provided new mechanistic targets in BPD pathogenesis and have challenged the paradigm related to the role of TGFβ up-regulation in neonatal lung injury.

MD: Indiana University School of Medicine, Indianapolis, IN, 2005.

Residency: Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.

Fellowship: Neonatal-Perinatal Medicine, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.

Certification: General Pediatrics, 2008; Neonatal and Perinatal Medicine, 2012.

Ahlfeld SK, Wang J, Gao Y, Snider P, Conway SJ. Initial suppression of transforming growth factor-β signaling and loss of TGFBI causes early alveolar structural defects resulting in bronchopulmonary dysplasia. Am J Pathol. 2016.

Goss KN, Tepper RS, Lahm T, Ahlfeld SK. Increased Cardiac Output and Preserved Gas Exchange Despite Decreased Alveolar Surface Area in Rats Exposed to Neonatal Hyperoxia and Adult Hypoxia. Am J Respir Cell Mol Biol. 2015;53(6):902-6.

Goss KN, Cucci AR, Fisher AJ, Albrecht M, Frump A, Tursunova R, Gao Y, Brown MB, Petrache I, Tepper RS, *Ahlfeld SK, *Lahm T. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure. Am J Physiol Lung Cell Mol Physiol. 2015 Apr 15;308(8):L797-806. (* co-senior authorship).

Assaf SJ, Chang DV, Tiller CJ, Kisling JA, Case J, Mund JA, Slaven JE, Yu Z, Ahlfeld SK, Poindexter B, Haneline LS, Ingram DA, Tepper RS. Lung Parenchymal Development in Premature Infants without Bronchopulmonary Dysplasia. Pediatr Pulmonol. 2015;50(12):1313-9.

Beam K, Aliaga S, Ahlfeld S, Cohen-Wolkowiez M, Smith P, Laughon M. A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants. J Perinatol. 2014;34(9):705-10.

Ahlfeld SK, Gao Y, Conway SJ, Tepper RS. Relationship of Structural to Functional Impairment during Alveolar-Capillary Membrane Development. Am J Pathol. 2015;185(4):913-9.

Ahlfeld SK, Conway SJ. Assessment of Inhibited Alveolar-Capillary Membrane Structural Development and Function in Bronchopulmonary Dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100(3):168-79.

Ahlfeld SK, Gao Y, Wang J, Horgusluoglu E, Bolanis E, Clapp DW, Conway SJ. Periostin down-regulation is an early marker of inhibited neonatal murine lung alveolar septation. Birth Defects Res A Clin Mol Teratol. 2013;97(6):373-85.

Ahlfeld SK, Conway SJ. Aberrant signaling pathways of the lung mesenchyme and their contributions to the pathogenesis of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2012;94(1):3-15.

Sehra S, Yao W, Nguyen ET, Ahyi AN, Barbé Tuana FM, Ahlfeld SK, Snider P, Tepper RS, Petrache I, Conway SJ, Kaplan MH. Periostin regulates goblet cell metaplasia in a model of allergic airway inflammation. J Immunol. 2011;186(8):4959-66.

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.

Sandip Bhattacharyya, MSc, PhD Member, Center for the Prevention of Preterm Birth

is an immunologist, who has basic science research programs in inflammation biology and signal transduction. The major research interest of Dr. Bhattacharyya’s laboratory is to understand the molecular mechanisms of glucocorticoid action in innate immunity and define context-specific immunomodulatory functions.

513-803-8039 sandip.bhattacharyya@cchmc.org

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Sandip Bhattacharyya, MSc, PhD

Member, Center for the Prevention of Preterm Birth

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-8039

Email sandip.bhattacharyya@cchmc.org

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Inflammation Immunology; signal transduction

Biography

Dr. Bhattacharyya received his doctoral degree in immunology and cell biology from Jadavpur University, India. His doctoral research shed light on multi-level regulation of host immune responses in experimental visceral leishmaniasis. During his post-doctoral training at the University of North Carolina, Chapel Hill, Dr. Bhattacharyya explored critical roles of Interleukin-10 for regulation of nuclear factor kappa B signaling pathway in dendritic cells. Later, at Washington University, St Louis and Vanderbilt University, Nashville, Dr. Bhattacharyya uncovered new mechanisms for glucocorticoid actions on Toll-like receptor-induced inflammatory pathways. His findings provided evidence for signal-dependent glucocorticoid sensitivity. Dr. Bhattacharyya’s study indicated that the spectrum of TLRs activated determines their responsiveness to steroid therapy.

Dr. Bhattacharyya was selected for the Ramanujan Fellowship, 2011, awarded by the Department of Science and Technology, Government of India.

BSc: Chemistry, University of Calcutta, Calcutta, India.

MSc: Biochemistry, University of Calcutta, Calcutta, India.

PhD: Cell Biology and Immunology, Jadavpur University, Calcutta, India.

Post Doctoral Fellowship: University of North Carolina, Chapel Hill, NC.

Senior Scientist: Washington University, Saint Louis, MO / Vanderbilt University, Nashville, TN.

Ratajczak C.K., Asada M, Allen, G.C., McMahon, D.G., Muglia, L.M., Smith, D., Bhattacharyya, S., and Muglia, L.J. Generation of myometrium-specific Bmal1 knockout mice for parturition analysis. Reproduction, Fertility and Development. 2012;24(5):759-67.

Bhattacharyya S, Kay T, Zhao Z, Muglia LJ. Glucocorticoids Target suppressor of cytokine synthesis 1 (SOCS1) and Type 1 Interferons to Regulate Toll-like Receptor-induced STAT1 Activation. Proc Natl Acad Sci USA. 2011;108(23):9554-9559.

Bhattacharyya, S, Ratajczak CK, Vogt SE, Kelley C, Colonna M, Schreiber RD. Muglia, LJ. TAK1 Targeting by Glucocorticoids Determines JNK and IkB Regulation in Toll-like Receptor-Stimulated Macrophages. Blood. 2010;115(10):1921-1931.

Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL. Glucocorticoids and the osteoclast. Ann N Y Acad Sci. 2007;1116:335-339.

Bhattacharyya S, Brown DE, Brewer JA, Vogt SE, Muglia LJ. Glucocorticoid receptor regulates toll-like receptor-4 mediated inflammatory responses by inhibition of p38 MAP kinase. Blood. 2007;109(10):4313-4319.

Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006;116(8):2152-2160.

Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS Jr., Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood. 2004;104(4):1100-1109.

Sen P, Bhattacharyya S, Wallet M, Wong CP, Poligone B, Sen M, Baldwin AS, Jr., Tisch, R. NF-kappa B hyperactivation has differential effects on the APC function of nonobese diabetic mouse macrophages. J Immunol. 2003;170(4):1770-1780.

Bhattacharyya S, Ghosh S, Dasgupta B, Mazumder D, Roy S, Majumdar S. Chemokine-induced leishmanicidal activity in murine macrophages via the generation of nitric oxide. J Infect Dis. 2002;185(12):1704-1708.

Bhattacharyya S, Ghosh S, Jhonson PL, Bhattacharya SK, and Majumdar S. Immunomodulatory role of interleukin-10 in visceral leishmaniasis: defective activation of protein kinase C-mediated signal transduction events. Infect Immun. 2001;69(3):1499-1507.

James P. Bridges, PhD

Visit the Bridges Lab.

513-636-0337 james.bridges@cchmc.org

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James P. Bridges, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-0337

Fax 513-636-7868

Email james.bridges@cchmc.org

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Airway smooth muscle remodeling in chronic lung disease; identification/function of HIF target genes in pulmonary epithelium; transcriptional control of epithelial plasticity during lung Injury/remodeling

Visit the Bridges Lab.

Biography

James Bridges, PhD, investigates the role of hypoxia inducible factors (HIFs) and downstream gene targets in chronic lung disease. These goals are achieved by utilizing both gain and loss-of-function mouse models to evaluate the mechanistic basis underlying the pathophysiologic changes in pulmonary function associated with altered HIF activity.

BS: Biochemistry, University of Colorado at Boulder, CO, 1995.

PhD: Molecular and Developmental Biology, University of Cincinnati, Cincinnati, OH, 2005.

Post-doctoral training: Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2010.

Bridges JP, Ikegami M, Mason RJ, Shannon JM. LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. Journal of Clinical Investigation. 2010; 120(5):1736.

Wang M, Bridges JP, Na CL, Xu Y, Weaver TE. The Meckel-Gruber Syndrome Protein MKS3 is Required for ER-Associated Degradation of Surfactant Protein C. Journal of Biological Chemistry. 2009; 284:33377-83.

Ahmad A, Ahmad S, Glover L, Miller S, Shannon JM, Guo X, Franklin WA, Bridges JP, Schaack JB, Colgan SP, White CW. Adenosine A2A receptor is a unique angiogenic target of HIF-2α in pulmonary endothelial cells. Proc Natl Acad Sci. 2009; 106(26):10684-9.

Dong M, Bridges JP, Apsley K, Xu Y, Weaver TE. ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C. Molecular Biology of the Cell. 2008; 19(6):2620-2630.

Bridges JP, Panos RJ. Surfactant Protein C related Interstitial Lung Disease. In: McCormack FX, Rounds S, eds. Molecular Basis of Pulmonary Disease: Insights from Rare Lung Disorders. Totowa, NJ: Humana, 2008.

Joseph Crisalli, MD

513-636-6771 sleep@cchmc.org

Hitesh Deshmukh, MD, PhD

and his laboratory focuses on the role of intestinal commensal bacteria in development of appropriate innate immune responses to pathogens in neonates. The ultimate goal of this research is to develop novel therapeutic approaches to decrease mortality in premature babies, one of the most vulnerable groups.

513-803-7448 hitesh.deshmukh@cchmc.org

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Hitesh Deshmukh, MD, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-7448

Email hitesh.deshmukh@cchmc.org

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MB; BS: University of Mumbai, Mumbai, India, 2001.

PhD: University of Cincinnati, Cincinnati, OH, 2006.

Residency: Pediatrics, State University of New York at Buffalo, Buffalo, NY, 2011.

Fellowship: Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 2014.

Certification: American Board of Pediatrics, 2012.

Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O'Leary CE, et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nature Medicine. 2014 Apr 20.

Yan QS, Sharma-Kuinkel BK, Deshmukh HS, Tsalik EL, Cr DD, Lucas JA et al. Dusp3 and Psme3 Are Associated with Murine Susceptibility to Staphylococcus aureus Infection and Human Sepsis. Plos Pathogens. 2014 Jun 5;10(6).

Deshmukh HS, Lioy J. The use of early lung biopsy in detection of fatal pulmonary disease in the neonate. The Journal of Pediatrics. 2014 Apr;164(4):934-6.

Deshmukh HS, Caty MG, Ryan RM, Lakshminrusimha S. Intermittent 'bulge' in the umbilical cord. Journal of Perinatology. 2010 Jul;30(7):500-2.

Ahn SH, Deshmukh HS8, Johnson N, Cowell LG, Rude TH, Scott WK, et al. Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses. PLoS Pathogens. 2010;6(9):e1001088. *co-first author.

Deshmukh HS, McLachlan A, Atkinson JJ, Hardie WD, Korfhagen TR, Dietsch M, et al. Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production. American Journal of Respiratory and Critical Care Medicine. 2009 Nov 1;180(9):834-45.

Deshmukh HS, Hamburger JB, Ahn SH, McCafferty DG, Yang SR, Fowler VG, Jr. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infection and immunity. 2009 Apr;77(4):1376-82.

Deshmukh HS, Shaver C, Case LM, Dietsch M, Wesselkamper SC, Hardie WD, et al. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. American Journal of Respiratory Cell and Molecular Biology. 2008 Apr;38(4):446-54.

Campbell SJ, Deshmukh HS*, Nelson CL, Bae IG, Stryjewski ME, Federspiel JJ, et al. Genotypic characteristics of Staphylococcus aureus isolates from a multinational trial of complicated skin and skin structure infections. Journal of Clinical Microbiology. 2008 Feb;46(2):678-84. *co-first author.

Deshmukh HS, Case LM, Wesselkamper SC, Borchers MT, Martin LD, Shertzer HG, et al. Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation. American Journal of Respiratory and Critical Care Medicine. 2005 Feb 15;171(4):305-14.

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

investigates the developmental biology of pulmonary vascular development, including how vascular endothelial growth factor (VEGF) mediates pulmonary vascular, lymphatic and airway development. He studies how VEGF mediates organization of pulmonary vasculature during late fetal life as well as how certain proteins implicated in axonal guidance during central nervous system development also direct developmental processes in the lung.

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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Clinical Interests

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.

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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Clinical Interests

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.

Eric S. Hall, PhD

participates in a number of interdisciplinary teams investigating prematurity and neonatal disease. Along with coordinating data collection and exchange efforts, his work involves the application of knowledge discovery techniques to clinical data sets, as well as the development of software tools to assist in the summarization of clinical data and the modeling of clinical processes.

513-803-2083 eric.hall@cchmc.org

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Eric S. Hall, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-2083

Fax 513-803-0968

Email eric.hall@cchmc.org

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Biomedical informatics; clinical informatics; data linkage; infant mortality; maternal child health; neonatal abstinence syndrome; preterm birth; public health informatics

Biography

Eric S. Hall, PhD, is a biomedical informaticist and researcher focused on improving perinatal health outcomes in at-risk populations. Dr. Hall currently leads data management and integration supporting research and quality improvement within the Cincinnati Children's Hospital Medical Center Perinatal Institute.

Dr. Hall's primary interests involve the linkage and integration of disparate data sets to facilitate the analysis of high-risk populations. These maternal and child health data include hospital electronic health records, vital records, geospatially-based measures from the American Communities Survey and other public data resources, and measures collected by community-based programs. While his principal focus has been on preterm birth and infant mortality reduction, Dr. Hall's interests extend to other high-risk maternal and child populations including those affected by withdrawal following in utero exposure to narcotics.

Dr. Hall has participated as a key member of many interdisciplinary teams within the Perinatal Institute and as part of multi-institutional collaborations. He is also the director of data analysis and management for Cradle Cincinnati, a collective impact collaborative to reduce infant mortality in Hamilton County, Ohio.

PhD: University of Utah, Salt Lake City, UT, 2008.

MS: Brigham Young University, Provo, UT, 2003.

BS: Brigham Young University, Provo, UT, 2001.

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Li Q, Kirkendall ES, Hall ES, Ni Y, Lingren T, Kaiser M, Lingren N, Zhai H, Solti I, Melton K. Automated Detection of Medication Administration Errors in Neonatal Intensive Care. J Biomed Inform. 2015 Jul 16.

Hall ES, Wexelblatt SL, Crowley M, Grow JL, Jasin LR, Klebanoff MA, McClead RE, Meinzen-Derr J, Mohan VK, Stein H, Walsh MC. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014 Aug;134(2):e527-34.

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

Goyal NK, Hall ES, Ammerman RT, Meinzen-Derr JK, Jones DE, Short JA, Van Ginkel JB. Association of maternal and community factors with enrollment in home visiting among at-risk, first time mothers. Am J Public Health. 2014 Feb;104 Suppl 1:S144-51.

Hall ES, Goyal NK, Ammerman RT, Miller M, Jones DE, Short JA, Van Ginkel JB. Development of a linked perinatal data resource from state administrative and community-based program data. Matern Child Health J. 2014 Jan;18(1):316-25.

Goyal NK, Hall ES, Meinzen-Derr JK, Kahn RS, Short JA, Van Ginkel JB, Ammerman RT. Dosage effect of prenatal home visiting on pregnancy outcomes in at-risk, first-time mothers. Pediatrics. 2013 Nov;132 Suppl 2:S118-25.

South AP, Jones DE, Hall ES, Huo S, Meinzen-Derr J, Liu L, Greenberg JM. Spatial analysis of preterm birth demonstrates opportunities for targeted intervention. Matern Child Health J. 2012 Feb;16(2):470-8.

Hall ES, Poynton MR, Narus SP, Jones SS, Evans RS, Varner MW, Thornton SN. Patient-level analysis of outcomes using structured labor and delivery data. J Biomed Inform. 2009 Aug;42(4):702-9.

Hall ES, Poynton MR, Narus SP, Thornton SN. Modeling the distribution of Nursing Effort using structured Labor and Delivery documentation. J Biomed Inform. 2008 Dec;41(6):1001-8.

Hall ES, Vawdrey DK, Knutson CD, Archibald JK. Enabling remote access to personal electronic medical records. IEEE Eng Med Biol Mag. 2003 May-Jun;22(3):133-9.

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

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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.

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

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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.

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.

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

Visit the Kalinichenko Lab.

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

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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Visit the Kalinichenko Lab.

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.

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.

Yutaka Maeda, DVM, PhD

is interested in understanding the mechanisms of transcriptional regulation in lung diseases, including lung cancer and asthma.

513-636-3322 yutaka.maeda@cchmc.org

Yutaka Maeda, DVM, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-3322

Email yutaka.maeda@cchmc.org

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Lung cancer; asthma

DVM: Hokkaido University, Sapporo, Japan, 1997.

PhD: University of California, Riverside, CA, 2002.

Maeda Y, Tsuchiya T, Hao H, Tompkins DH, Xu Y, Mucenski ML, Du L, Keiser AR, Fukazawa T, Naomoto Y, Nagayasu T, Whitsett JA. Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung. J Clin Invest. 2012 Dec 3;122(12):4388-400.

Whitsett JA, Haitchi HM, Maeda Y. Intersections between pulmonary development and disease. Am J Respir Crit Care Med. 2011 Aug 15;184(4):401-6.

Maeda Y, Chen G, Xu Y, Haitchi HM, Du L, Keiser AR, Howarth PH, Davies DE, Holgate ST, Whitsett JA. Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation. Am J Respir Crit Care Med. 2011 Aug 15;184(4):421-9.

Fukazawa T, Maeda Y, Matsuoka J, Ono T, Mominoki K, Yamatsuji T, Shigemitsu K, Morita I, Murakami I, Tanaka H, Durbin ML, Naomoto Y. Targeting KRAS mutation-bearing lung cancer in vivo by pulmonary surfactant-adenovirus-mediated gene transfer. Anticancer Res. 2010 Dec;30(12):4925-35.

Han S, Fukazawa T, Yamatsuji T, Matsuoka J, Miyachi H, Maeda Y, Durbin M, Naomoto Y. Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and retinoic acids. PLoS One. 2010 Nov 4;5(11):e13834.

Fukazawa T, Maeda Y, Matsuoka J, Yamatsuji T, Shigemitsu K, Morita I, Faiola F, Durbin ML, Soucek L, Naomoto Y. Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc. Anticancer Res. .2010 Oct;30(10):4193-200.

Fukazawa T, Matsuoka J, Yamatsuji T, Maeda Y, Durbin ML, Naomoto Y. Adenovirus-mediated cancer gene therapy and virotherapy (Review). Int J Mol Med. 2010 Jan;25(1):3-10.

Fukazawa T, Maeda Y, Matsuoka J, Tanaka N, Tanaka H, Durbin ML, Naomoto Y. Drug-regulatable cancer cell death induced by BID under control of the tissue-specific, lung cancer-targeted TTS promoter system. Int J Cancer. 2009 Oct 15;125(8):1975-84.

Fukazawa T, Matsuoka J, Naomoto Y, Maeda Y, Durbin ML, Tanaka N. Malignant pleural mesothelioma-targeted CREBBP/EP300 inhibitory protein 1 promoter system for gene therapy and virotherapy. Cancer Res. 2008 Sep 1;68(17):7120-9.

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

Show All

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 K, Akinbi HT. Neonatal jaundice. Strategies to reduce bilirubin-induced complications. Postgrad Med. 1999 Nov;106(6):167-8, 171-4, 177-8.

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

Show All

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.

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

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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

Show All

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

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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

Show All

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

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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

Show All

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.

Johnson RF, Cohen AP, Guo Y, Schibler K, Greinwald JH. Genetic mutations and aminoglycoside-induced ototoxicity in neonates. Otolaryngol Head Neck Surg. 2010 May;142(5):704-7.

Olsen IE, Lawson ML, Meinzen-Derr J, Sapsford AL, Schibler KR, Donovan EF, Morrow AL. Use of a body proportionality index for growth assessment of preterm infants. J Pediatr. 2009 Apr;154(4):486-91.

Lavery AP, Meinzen-Derr JK, Anderson E, Ma Q, Bennett MR, Devarajan P, Schibler KR. Urinary NGAL in premature infants. Pediatr Res. 2008 Oct;64(4):423-8.

Schibler KR, Georgelas A, Rigaa A. Developmental biology of the dendritic cell system. Acta Paediatr Suppl. 2002;91(438):9-16.

Book Chapters

Schibler KR. Developmental Biology of the Hematopoietic Growth Factors. In Fetal and Neonatal Physiology. Polin RA, Fox WW, eds. Philadelphia: WB Saunders, 2009.

Schibler KR. The Mononuclear Phagocyte System. In Fetal and Neonatal Physiology. Polin RA, Fox WW, eds. Philadelphia: WB Saunders, 2009.

Donovan E, Greenberg J, Habernman B, Narendran V, Schibler K, Warner B. Neonatal Morbidities of Prenatal and Perinatal Origin. In Maternal-Fetal Medicine. Creasy RK, Resnik R and Iams JD., eds Philadelphia : WB Saunders, 2009.

John Shannon, PhD

studies the elucidation of molecular mechanisms that regulate morphogenesis and differentiation of the lung epithelium and mesenchyme. A major focus of the lab is the role of fibroblast growth factors and epithelial-mesenchymal signaling pathways in the regulation of branching morphogenesis in the developing lung.

513-636-2938 john.shannon@cchmc.org

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John Shannon, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-2938

Fax 513-636-7868

Email john.shannon@cchmc.org

Show All

Clinical

Lung morphogenesis and differentiation; isolation and characterization of genes differentially expressed in the developing lung; maintenance of alveolar lung cell differentiation; pulmonary vascular development; congenital diaphragmatic hernia

Research

Elucidation of the molecular mechanisms that regulate morphogenesis; differentiation of the lung epithelium

AB: Biology, University of California, Santa Cruz, CA, 1972.

PhD: University of California, Berkeley, CA, 1979.

Bridges JP, Ikegami M, Brilli LL, Chen X, Mason RJ, Shannon JM. LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. J Clin Invest. 2010 May 3;120(5):1736-48.

Ahmad A, Ahmad S, Glover L, Miller SM, Shannon JM, Guo X, Franklin WA, Bridges JP, Schaack JB, Colgan SP, White CW. Adenosine A2A receptor is a unique angiogenic target of HIF-2alpha in pulmonary endothelial cells. Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10684-9.

Metzger DE, Stahlman MT, Shannon JM. Misexpression of ELF5 disrupts lung branching and inhibits epithelial differentiation. Dev Biol. 2008 Aug 1;320(1):149-60.

Lin S, Ikegami M, Xu Y, Bosserhoff AK, Malkinson AM, Shannon JM. Misexpression of MIA disrupts lung morphogenesis and causes neonatal death. Dev Biol. 2008 Apr 15;316(2):441-55.

Metzger DE, Xu Y, Shannon JM. Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung. Dev Dyn. 2007 May;236(5):1175-92.

Chen X, Hyatt BA, Mucenski ML, Mason RJ, Shannon JM. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11724-9.

Asikainen TM, Chang LY, Coalson JJ, Schneider BK, Waleh NS, Ikegami M, Shannon JM, Winter VT, Grubb P, Clyman RI, Yoder BA, Crapo JD, White CW. Improved lung growth and function through hypoxia-inducible factor in primate chronic lung disease of prematurity. FASEB J. 2006 Aug;20(10):1698-700.

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.

Portnoy J, Pan T, Dinarello CA, Shannon JM, Westcott JY, Zhang L, Mason RJ. Alveolar type II cells inhibit fibroblast proliferation: role of IL-1alpha. Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L307-16.

Debora I. Sinner, PhD

is interested in understanding the molecular mechanisms underlying foregut formation. Specifically, her lab focuses on the molecular mechanism underlying lung and upper airway development and the paracrine interactions between epithelium and mesenchyme. Ultimately, her goal is to use the embryo as a paradigm to understand diseases affecting upper airway and lung. To this end her lab utilizes knockout mouse models and the frog embryo combined with molecular and cellular approaches using in vitro systems.

513-803-1353 debora.sinner@cchmc.org

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Debora I. Sinner, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-1353

Email debora.sinner@cchmc.org

Show All

Developmental biology; pulmonary biology

Visit the Sinner Lab.

Biography

Debora Sinner, PhD, obtained her doctoral degree from University of Buenos Aires, Argentina. Her dissertation focused on the effects of maternal diabetes during murine embryonic development and role of prostaglandins and reactive species of oxygen in glucose induced abnormal development. As a postdoctoral trainee in the Division of Developmental Biology at Cincinnati Children's, Dr. Sinner focused on the molecular mechanisms underlying endoderm formation, the germ layer that gives rise to the gastrointestinal tract. Under the direction of her mentor, Aaron Zorn, PhD, we identified a mechanism by which Sox proteins regulate the Wnt signaling pathway during frog development. These findings are relevant since Wnt signaling pathway has been linked to development and disease.

After completion of her doctoral training, Dr. Sinner accepted a faculty position in the Division of Neonatology and Pulmonary Biology at Cincinnati Children's within the UC Department of Pediatrics. Her current research focuses on upper airway and lung development. Dr. Sinner's lab is studying how paracrine Wnt signaling controls the differentiation of pulmonary cells lineages, including the microvasculature and airway cartilage.

MS: University of Buenos Aires, Argentina, 1999.

PhD: University of Buenos Aires, Argentina, 2003.

Post doctoral training: Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2003-2009.

Kormish JD, Sinner D, Zorn AM. Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Dev Dyn. 2010 Jan;239(1):56-68.

Sinner D, Kordich JJ, Opoka R Rankin SA,. Lin S-J, Jonatan D, Zorn AM, Wells JM. Beta-catenin/Tcf activity is repressed by Sox17 and enhanced by Sox4 in colon carcinoma cells. Mol Cell Biol. 2007;27:7802-7815.

Sinner D, Kirilenko P, Rankin S, Wei E, Howard L, Kofron M, Heasman J, Woodland HR, Zorn AM. Global analysis of the transcriptional network controlling Xenopus endoderm formation. Development. 2006 May;133(10):1955-66.

Sinner D, Rankin S, Lee M, Zorn AM. Sox17 and beta-catenin cooperate to regulate the transcription of endodermal genes. Development. 2004 Jul;131(13):3069-80.

Sinner D, Caviglia JM, Jawerbaum A, Igal RA, Gonzalez E. Lipid metabolism in the embryos of diabetic rats during early organogenesis: modulatory effect of prostaglandin E2. Reprod Fertil Dev. 2003;15(1-2):75-80.

Grants

Molecular mechanisms underlying upper airway patterning and tracheomalacia. National Institutes of Health/National Heart, Lung, and Blood Institute. Aug 2012-Jul 2017. K01.

Daniel T. Swarr, MD

investigates epigenetic regulation of gene expression during early endoderm and lung development, and is particularly interested in the role that long non-coding RNAs (lncRNAs) play during development and disease. The goal of his research is to provide insights into the pathogenesis of congenital malformations and pulmonary disorders.

513-803-8396 daniel.swarr@cchmc.org

Daniel T. Swarr, MD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-8396

Email daniel.swarr@cchmc.org

Show All

Clinical

Isolated and syndromic birth defects; bronchopulmonary dysplasia; pediatric lung diseases; general neonatology

Research

Early endoderm and lung development; epigenetic regulation of gene expression; long non-coding RNAs; Congenital lung malformations; TEF/EA; VACTERL

Biography

After finishing general pediatrics residency training at Baylor College of Medicine, Dr. Swarr completed a combined fellowship program at The Children’s Hospital of Philadelphia, which lead to Board certification in Neonatal-Perinatal Medicine and Medical Genetics & Genomics. As both a neonatologist and geneticist, Dr. Swarr is particularly interested in both isolated and syndromic birth defects impacting the health of newborn infants.

The goal of Dr. Swarr’s research is to improve our understanding of the etiology and pathogenesis of congenital malformations and pulmonary disease using a wide variety of tools from developmental biology, genetics and epigenetics. His laboratory is particularly interested in understanding epigenetic mechanisms by which gene expression is regulated during early endoderm and lung development, and how disruptions of these processes lead to neonatal disease. Current work seeks to define the role of long non-coding RNAs (lncRNAs) during lung development and lung epithelial repair after injury.

Dr. Swarr’s laboratory is also actively involved in “translating” findings from basic developmental biology to better understanding disorders of the esophagus, trachea, and lungs through a patient registry-biorepository established in collaboration with investigators at CCHMC and The Children’s Hospital of Philadelphia.

MD: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 2007.

Residency: General Pediatrics, Baylor College of Medicine & Texas Children’s Hospital, Houston, TX, 2007-2010.

Fellowship: Combined Fellowship in Neonatal-Perinatal Medicine and Medical Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, 2010-2015.

Board Certifications: General Pediatrics, 2010; Medical Genetics & Genomics, 2015; Neonatal-Perinatal Medicine, 2016.

Swarr DT, Morrisey EE. Lung endoderm morphogenesis: gasping for form and function. Annu Rev Cell Dev Biol. 2015 Nov 13;31:553-73.

Luo M, Mulchandani S, Dubbs HA, Swarr DT, Pyle L, Zackai EH, Spinner NP, Conlin LK. Detection of mutually exclusive mosaicism in a girl with genotype-phenotype discrepancies. Am J Med Genet A. 2015 Dec;167A(12):3091-5.

Kruska P, Li D, Harr MH, Wilson NR, Swarr D, McCormick E, Chiavacci R, Li M, Johnson J, McDonald-McGinn D, Deardorff M, Falk MJ, Allanson J, Saadi I, Hakonarson H, Muenke M, Zackai EH. Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome. J Med Genet. 2015 Feb;52(2):104-10.

Herriges M*, Swarr DT*, Morley MP, Peng T, Stewart KM, Morrisey EE. Long non-coding RNAs are preferentially located near transcription factors and regulate lung development. Genes Dev. 2014 Jun 15;28(12):1363-79. *Co-first authors

Wenger TL, Gerdes J, Deardorff MA, Taub K, Swarr DT, Abend N. Telemedicine for genetic and neurologic evaluation of infants in the Neonatal Intensive Care Unit. J Perinatol. 2014 Mar;34(3):234-40.

Swarr DT, Khalek N, Treat J, Horton M, Riviere JB, Dobyns W, Zackai EH. Expanding the differential diagnosis of fetal hydrops: an unusual prenatal presentation of megalencephaly-capillary malformation syndrome. Prenat Diagn. 2013 Oct;33(10):1010-2.

Kalish JM, Conlin LK, Bhatti TR, Feret H, Harris MC, Izumi K, Mostoufi-Moab S, Saitta S, States LJ, Swarr DT, Wilkens AB, Zackai EH, Zelley K, Bartolomei MS, Nichols KE, Palladino AA, Spinner NB, Deardorff MA. Clinical presentation of three subjects with genome-wide paternal uniparental disomy. Am J Med Genet A. 2013 Mar;161(3):473-8.

Sen P, Yang Y, Navarro C, Silva I, Szafranski P, Kolodziejska KE, Dharmadhikari AV, Kozakewich H, Kearney D, Cahill JB, Whitt M, Bilic M, Margraf L, Charles A, Goldblatt J, Gibson K, Lantz P, Garvin J, Petty J, Kiblawi Z, Zuppan C, McConkie-Rosell A, McDonald MT, Peterson-Carmichael SL, Gaede JT, Shivanna B, Schady D, Friedlich PS, Hays SR, Valenzuela Palafoll I, Siebers-Renelt U, Bohring A, Finn LS, Siebert JR, Galambos C, Nguyen L, Riley M, Chassaing N, Vigouroux A, Rocha G, Fernandes S, Brumbaugh J, Roberts K, Homing L, Lo I, Lam S, Gerychova R, Jezova M, Valaskova I, Fellman F, Afshar K, Giannoni E, Muehlethaler V, Liang J, Lioy J, Deshmukh H, Srinivasan L, Swarr DT, Sloman M, Shaw-Smith C, van Loon L, Hagman C, Sznajer Y, Barrea C, Galant C, Detaille T, Wambach J, Cole JS, Hamvas A, Prince L, Langston C, Welty S, Stankiewicz P. Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain. Hum Mutat. 2013 June;34(6):801-11.

Nathanson J, Swarr DT, Singer A, Liu M, Chinn A, Jones W, Hurst J, Khalek N, Zackai E, Slavotinek A. Novel FREM1 mutations expand the phenotypic spectrum associated with Manitoba-Oculo-Tricho-Anal (MOTA) syndrome and Bifid Nose Renal Agenesis Anorectal Malformations (BNAR) syndrome. Am J Med Genet A. 2013 Mar;161(3):473-8.

Swarr DT, Bloom D, Lewis RA, Elenberg E, Friedman EM, Glotzbach C, Wissman SD, Shaffer LG, Potocki L. Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the literature, and proposals for medical management. Am J Med Genet A. 2010 Mar;152A(3):565-72.

Bruce C. Trapnell, MS, MD Assistant Director, Adult Cystic Fibrosis Center

seeks to define mechanisms regulating innate immunity and inflammation in the lungs. His major focus is alveolar macrophage function in health and disease and the regulation alveolar homeostasis and host defense by GM-CSF in health and disease.

513-636-6361 bruce.trapnell@cchmc.org

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Bruce C. Trapnell, MS, MD

Assistant Director, Adult Cystic Fibrosis Center

Attending Physician

Pulmonologist - Research, Adult Clinical, Division of Pulmonary Medicine

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-6361

Fax 513-636-3723

Email bruce.trapnell@cchmc.org

Show All

Clinical

Pulmonary alveolar proteinosis; cystic fibrosis; alpha-1 antitrypsin deficiency; other rare lung disorders

Research

Alveolar macrophage function; molecular techniques using gene knockout, transgenic and conditional gene expression mouse models and non-human primates, in vitro and in vivo viral gene transfer, and bone marrow transplantation

Biography

Bruce Trapnell, MS, MD, received his medical degree from the University of Maryland in 1985, and completed a medical residency at The Ohio State University Hospitals and a fellowship in pulmonary medicine at the Clinical Center of the National Institutes of Health, where he then served as senior attending physician. Subsequently, he established the Division of Pulmonary and Virology Studies at Genetic Therapy, Inc., a subsidiary of Novartis, Pharma, serving as vice president before joining Cincinnati Children’s Hospital Medical Center, where he is now full professor for the UC College of Medicine.

Dr. Trapnell has conducted lung disease research since his training and has been continuously funded by the NIH since 2001, shortly after his arrival in Cincinnati. He has published over 90 original articles and has trained more than 16 post-doctoral fellows. Dr. Trapnell’s research interests are focused to the pathogenesis and therapy of rare lung diseases and mechanisms by which GM-CSF regulates innate immunity and lung host defense.

Dr. Trapnell is director of Cincinnati’s Cystic Fibrosis Therapeutics Development Network Center, assistant director of the Adult Cystic Fibrosis Care Center, director of the Rare Lung Diseases Clinical Research Consortium, scientific director of the Pulmonary Alveolar Proteinosis Foundation. Dr. Trapnell is the past scientific director of the Alpha-1 Foundation, for which he organized and directed the grant program for eight years.

MS: Genetics, The George Washington University, Washington, DC, 1981.

MD: University of Maryland School of Medicine, Baltimore, MD, 1984.

Residency: Internal Medicine, The Ohio State University Hospitals, Columbus, OH, 1987.

Fellowship: Pulmonary Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, 1989.

Certification: Diplomate in Internal Medicine, American Board of Internal Medicine, 1987; Diplomate, National Board of Medical Examiners, 1987; Diplomate in Pulmonary Medicine, American Board of Internal Medicine, 2000.

Wu H, Suzuki T, Carey B, Trapnell BC, McCormack FX. Keratinocyte growth factor (KGF) augments pulmonary innate immunity through epithelium-driven, GM-CSF dependent paracrine activation of alveolar macrophages. J Biol Chem. 2011 Feb 22.

D'Mello S, Trauernicht A, Ryan A, Bonkowski E, Willson T, Trapnell BC, Frank SJ, Kugasathan S, Denson LA. Innate dysfunction promotes linear growth failure in pediatric Crohn's disease and growth hormone resistance in murine ileitis. Inflamm Bowel Dis. 2011 Feb 18.

Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS, Linehan WM, Hajjar F, Kinder BW, Trapnell BC, Bissler JJ, Franz DN, McCormack FX. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010 Sep;138(3):674-81.

Han X, Gilbert S, Groschwitz K, Hogan S, Jurickova I, Trapnell B, Samson C, Gully J. Loss of GM-CSF signalling in non-haematopoietic cells increases NSAID ileal injury. Gut. 2010 Aug;59(8):1066-78.

Carey B, Trapnell BC. The molecular basis of pulmonary alveolar proteinosis. Clin Immunol. 2010 May;135(2):223-35.

Trapnell BC, Maguiness K, Graff GR, Boyd D, Beckmann K, Caras S. Efficacy and safety of Creon 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis. J Cyst Fibros. 2009 Dec;8(6):370-7.

Trapnell BC, Carey BC, Uchida K, Suzuki T. Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages. Curr Opin Immunol. 2009 Oct;21(5):514-21.

Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, Stevens CA, Beck DC, Denson LA, Carey BC, Keicho N, Krischer JP, Yamada Y, Trapnell BC. Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. Blood. 2009 Mar 12;113(11):2547-56.

Susan E. Wert, PhD

studies lung development, injury, and repair as it pertains to molecular morphology (gene and protein expression in situ), ultrastructure, and histopathology of the developing and adult lung. In addition, she studies the histopathology of the human lung as it relates to interstitial lung disease, especially to genetic disorders of surfactant dysfunction in the neonatal and pediatric population.

513-636-4297 susan.wert@cchmc.org

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Susan E. Wert, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-4297

Fax 513-636-7868

Email susan.wert@cchmc.org

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Clinical

Structural morphology of the lung; tissue responses to acute and chronic lung injury; morphogenesis of the lung and the origin of pulmonary malformations; use of transgenic mouse models to study mechanisms of lung development, cytodifferentiation, injury and repair in the lung; development of molecular markers for the study of respiratory epithelial cell differentiation and for cell lineage studies; image analysis and morphometry

Research

Lung development, injury and repair as it pertains to molecular morphology (gene and protein expression in situ); ultrastructure, and histopathology of the developing and adult lung; the histopathology of the human lung as it relates to interstitial lung disease, especially to genetic disorders of surfactant dysfunction in the neonatal and pediatric population

PhD: Anatomy and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 1988.

Postdoctoral Fellowship: Perinatology, Division of Neonatology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 1988-1991.

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.

Besnard V, Matsuzaki Y, Clark JC, Xu Y, Wert SE, Ikegami M, Stahlman MT, Weaver TE, Hunt AN, Postle AD, Whitsett JA. Conditional Deletion of Abca3 in Alveolar Type II Cells Alters Surfactant Homeostasis in Newborn and Adult Mice. Am J Physiol Lung Cell Mol Physiol. 2010 Feb 26.

Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med. 2010;61:105-19. Review.

Tompkins DH, Besnard V, Lange AW, Wert SE, Keiser AR, Smith AN, Lang R, Whitsett JA. Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells. PLoS One. 2009 Dec 14;4(12):e8248.

Wert SE, Whitsett JA, Nogee LM. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol. 2009 Jul-Aug;12(4):253-74.

Kathryn A. Wikenheiser-Brokamp, MD, PhD Director, Residency Research Program

investigates pediatric and adult lung diseases, including cancer, which are characterized by aberrant epithelial cell growth and differentiation. A major focus is the molecular mechanisms underlying Rb/p16, p53, and Dicer1 pathway function in lung development and the pathogenesis of lung disease. The ultimate goal is to identify new diagnostic, prognostic and therapeutic targets for common pulmonary disorders.

513-803-0239 kathryn.wikenheiser-brokamp@cchmc.org

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Kathryn A. Wikenheiser-Brokamp, MD, PhD

Director, Residency Research Program

Associate Director, Medical Scientist Training Program

Academic Affiliations

Associate Professor, UC Department of Pathology & Laboratory Medicine

Phone 513-803-0239

Fax 513-636-7868

Email kathryn.wikenheiser-brokamp@cchmc.org

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Clinical Interests

Pathology; pulmonary pathology

BS: Mathematics/Natural Science, Secondary Education Minor, University of Mary, Bismarck, ND, 1988.

PhD: Developmental Biology, Developmental Biology and Medical Science Scholars Programs, University of Cincinnati, Cincinnati, OH, 1994.

MD: Medical Science Scholars Program, University of Cincinnati, Cincinnati, OH, 1996.

Residency: Anatomic Pathology, Department of Pathology and Immunology, Washington University-Barnes/Jewish Hospital, St. Louis, MO, 1996-2002.

Clinical Training/Postdoctoral Research: Department of Pathology and Immunology, Washington University, St. Louis, MO, 1999-2002.

Licensure: State of Ohio, 2003.

Certification: Anatomic Pathology, The American Board of Pathology, 1999.

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.

Adams AK, Hallenbeck GE, Casper KA, Patil YJ, Wilson KM, Kimple RJ, Lambert PF, Witte DP, Xiao W, Gillison ML, Wikenheiser-Brokamp KA, Wise-Draper TM, Wells SI. DEK promotes HPV-positive and -negative head and neck cancer cell proliferation. Oncogene. 2-14 Mar 10;0:1.

Cundiff WB, McCormack FX, Wikenheiser-Brokamp K, Starnes S, Kotloff R, Benzaquen S. Successful management of a chronic, refractory bronchopleural fistula with endobronchial valves followed by talc pleurodesis. Am J Respir Crit Care Med. 2014 Feb 15;189(4):490-1.

Akeno N, Miller AL, Ma X, Wikenheiser-Brokamp KA. p53 suppresses carcinoma progression by inhibiting mTOR pathway activation. Oncogene. 2014 Jan 27.

Zafar MA, McCormack FX, Rahman S, Tencza C, Wikenheiser-Brokamp KA, Young LR, Shizukuda Y, Elwing JM. Pulmonary vascular shunts in exercise-intolerant patients with lymphangioleiomyomatosis. Am J Respir Cri. Care Med. 2013 Nov 1;188(9):1167-70.

McCormack FX, Wilmott C, Young LR, Wikenheiser-Brokamp K. An atoll variant that mocks. Am J Respir Crit Care Med. 2013 Jul 1;188(1): 110.

Meraj R, Wikenheiser-Brokamp KA, Young LR, Byrnes S, McCormack FX. Utility of transbronchial biopsy in the diagnosis of lymphangioleiomyomatosis. Front Med. 2012 Dec;6(4); 395-405.

Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messenger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965.

Simpson DS, Mason-Richie NA, Gettler CA, Wikenheiser-Brokamp KA. Retinoblastoma family proteins have distinct functions in pulmonary epithelial cells in vivo critical for suppressing cell growth and tumorigenesis. Cancer Res. 2009 Nov 15;69(22):8733-41.

Mason-Richie NA, Mistry MJ, Gettler CA Elayyadi A, Wikenheiser-Brokamp KA. Retinoblastoma function is essential for establishing lung epithelial quiescence after injury. Cancer Res. 2008 Jun 1;68(11):4068-76.

Yan Xu, PhD Director of Bioinformatics Core, Neonatology & Pulmonary Biology; Perinatal Institute

has research interests that include the identification of gene signatures, regulatory networks and biological pathways controlling lung development, maturation and diseases. She is actively involved in the development of detailed developmental lung-map via high-throughput single cell genomics to provide useful tools and resources for the lung research community.

513-636-8921 yan.xu@cchmc.org

High Res

Yan Xu, PhD

Director of Bioinformatics Core, Neonatology & Pulmonary Biology; Perinatal Institute

Academic Affiliations

Professor, UC Department of Pediatrics

UC Department of Biomedical Informatics

Phone 513-636-8921

Fax 513-636-7868

Email yan.xu@cchmc.org

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Bioinformatics; systems biology application in pulmonary research; lung cell type specific signaling; asthma associated pathology

Biography

Dr. Xu's research interests are the identification of gene signatures, regulatory networks and biological pathways controlling lung development, maturation and diseases. She is actively involved in the development of detailed developmental lung-map via high-throughput single cell genomics to provide useful tools and resources for the lung research community.

BS: Pharmacology, Shanghai Medical University, China, 1986.

MS: Pathology, Shanghai Medical University, China, 1989.

PhD: Molecular and Cellular Pharmacology, University of South Alabama, Mobile, Alabama, 1997.

Du Y, Guo M, Whitsett JA, Xu Y. 'LungGENS': a web-based tool for mapping single-cell gene expression in the developing lung. Thorax. 2015 Jun 30.

Bridges JP, Schehr A, Wang Y, Huo L, Besnard V, Ikegami M, Whitsett JA, Xu Y. Epithelial SCAP/INSIG/SREBP Signaling Regulates Multiple Biological Processes During Perinatal Lung Maturation. PLoS One. 2014 May 7;9(5):e91376.

Xu Y, Wang Y, Besnard V, Ikegami M, Wert SE, Heffner C, Murray SA, Donahue LR, Whitsett JA. Transcriptional programs controlling perinatal lung maturation. PLoS One. 2012;7(8):e37046.

Xu Y, Whitsett JA. Functional Genomics - Transcriptional Networks Controlling Lung Maturation and Surfactant Homeostasis. Hutton J (Ed). Pediatric Biomedical Informatics: Computer Applications in Pediatric Research (Translational Bioinformatics). 2012. Publisher: Springer.

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;11(1):451.

Xu Y, Saegusa C, Schehr A, Grant S, Whitsett JA, Ikegami M. C/EBPa is required for pulmonary cytoprotection during hyperoxia. American journal of physiology. 2009;297(2):L286-298.

Xu Y, Ikegami M, Wang Y, Matsuzaki Y, Whitsett JA. Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells. BMC Genomics. 2007;8:455.

Xu Y, Liu C, Clark JC, Whitsett JA. Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(508) in the lung. J Biol Chem. 2006;281:11279-11291.

Wan H, Xu Y, Ikegami M, Stahlman MT, Kaestner KH, Ang SL, Whitsett JA. Foxa2 is required for transition to air breathing at birth. Proc Natl Acad Sci USA. 2004;101:14449-14454.

Xu Y, Clark JC, Aronow BJ, Dey CR, Liu C, Wooldridge JL, Whitsett JA. Transcriptional adaptation to cystic fibrosis transmembrane conductance regulator deficiency. J Biol Chem. 2003;278:7674-7682.

Grants