Child Health Research Career Development Award

Louis J. Muglia, MD, PhD Co-Director, Perinatal Institute 513-803-7902 louis.muglia@cchmc.org

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Louis J. Muglia, MD, PhD

Co-Director, Perinatal Institute

Director, Center for Prevention of Preterm Birth

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-7902

Email louis.muglia@cchmc.org

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Specialties

Pediatric endocrinology

Visit the Muglia Lab.

Biography

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Grants

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

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

Program Co-Directors

James E. Heubi, MD Director, Center for Clinical and Translational Science and Training 513-636-4415 james.heubi@cchmc.org

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James E. Heubi, MD

Director, Center for Clinical and Translational Science and Training

Associate Dean, Clinical and Translational Research

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4415

Fax 513-803-1039

Email james.heubi@cchmc.org

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Clinical & Research Interests

Clinical

Inflammatory bowel disease; cholestatic liver disease; malabsorption

Research

Cholesterol absorption; cholesterol metabolism; inborn errors of bile acid metabolism; bone metabolism in health and disease; TPN-related cholestasis and its treatment

Biography

James E. Heubi, MD, has been a practicing pediatric gastroenterologist since 1979, when he joined the staff at Cincinnati Children's Hospital Medical Center.

Dr. Heubi's practice includes the treatment of all disorders affecting the gastrointestinal tract, liver and biliary tract and pancreas.

Dr. Heubi's areas of practice interests include liver disease and complications related to end-stage liver disease and liver transplantation and the management of patients with "short gut" or compromised gut function requiring prolonged enteral or parenteral nutritional support.

Dr. Heubi is the associate dean for clinical research at the University of Cincinnati College of Medicine.

MD: Indiana University School of Medicine, Indianapolis, IN, 1973.

Residency: James Whitcomb Riley Hospital for Children, Indiana University, Indianapolis, IN, 1973 to 1975.

Fellowship: Children's Hospital Medical Center, Cincinnati, OH, 1975 to 1978.

Certification: Pediatric Gastroenterology and Nutrition, 1990.

View PubMed Publications

Heubi JE, Setchell KD, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2014 Aug 28.

Setchell KDR, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edressi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hoffman AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat soluble vitamin deficiency. Gastroenterology. 2013;144:945-955.

Mizukawa B, George A, Pushkaran S, Weckbach L, Kalinyak K, Heubi JE, Kalfa TA. Cooperating G6PD mutations associated with severe neonatal hyperbillirubinemia and cholestasis. Pediatr Blood Cancer. 2011 May;56(5):840-2.

Kohli R, Kirby M, Setchell KD, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D'Alessio DA, Shroyer NF, Seeley RJ. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G652-60.

Heubi, JE. Child health research and the Clinical Translational Science Awards: where have we been and where are we going? Clin Transl Sci. 2010 Jun;3(3):67-8.

Hommel KA, McGraw KL, Ammerman RT, Heubi JE, Hansen M, Dunlap E, Beidel DC. Psychosocial functioning in children and adolescents with gastrointestinal complaints and disorders. J Clin Psychol Med Settings. 2010 Jun;17(2):159-66.

Setchell KD, Zhao X, Jha P, Heubi JE, Brown NM. The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr. 2009 Oct;90(4):1029-37.

Wooldridge JL, Heubi JE, Amaro-Galvez R, Boas SR, Blake KV, Nasr SZ, Chatfield B, McColley SA, Woo MS, Hardy KA, Kravitz RM, Straforini C, Anelli M, Lee C. EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. J Cyst Fibros. 2009 Dec;8(6):405-17.

Graham RC, Heubi JE, Cohen MB, Li B. Teaching and tomorrow: a novel recruitment program for a pediatric subspecialty. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):594-8.

Burke KT, Horn PS, Tso P, Heubi JE, Woollett LA. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels. Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G144-51.

Jeffrey Robbins, PhD Executive Co-Director, Heart Institute 513-636-8098 jeffrey.robbins@cchmc.org

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Jeffrey Robbins, PhD

Executive Co-Director, Heart Institute

Director, Molecular Cardiovascular Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8098

Email jeffrey.robbins@cchmc.org

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Specialties

Structure function relationships for the contractile proteins; cardiac-specific gene manipulation in transgenic rabbits; the contractile protein myosin and human heart failure; molecular studies of human valve disease

Visit the Robbins Lab.

Biography

Jeff Robbins CV (.pdf)

Gupta MK, Robbins J. Post-translational control of cardiac hemodynamics through myosin binding protein C. Pflugers Arch: European journal of physiology. 2014 Feb;466(2):231-6.

Mun JY, Previs MJ, Yu HY, Gulick J, Tobacman LS, Beck Previs S, Robbins J, Warshaw DM, Craig R. Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2170-5.

Sandri M, Robbins J. Proteotoxicity: An underappreciated pathology in cardiac disease. J Mol Cell Cardiol. 2014 Jun;71c:3-10.

Wang X, Robbins J. Proteasomal and lysosomal protein degradation and heart disease. J Mol Cell Cardiol. 2014 Jun;71c:16-24.

James J, Robbins J. Ablating a cardiac protein: Causality at last. Circ Res. 2013;112:1415-1419.

Razzaque MA, Gupta M, Osinska H, Gulick J, Blaxall BC, Robbins J. An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure. Circ Res. 2013 Aug 16;113(5):553-61.

Gupta MK, Gulick J, James J, Osinska H, Lorenz JN, Robbins J. Functional dissection of myosin binding protein C phosphorylation. J Mol Cell Cardiol. 2013;64C:39-50.

Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest. 2013;123(12):5284-97.

Pattison JS, Robbins J. Desmin and heart disease. In: Kavallaris M, ed. Cytoskeleton and human disease. New York, NY: Humana Press; 2012:411-424.

Bhuiyan MS, Gulick J, Osinska H, Gupta M, Robbins J. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions. J Mol Cell Cardiol. 2012;53:838-847.

Grants

Cardiac Signaling in the Normal and Abnormal Heart. Principal Investigator. National Heart, Lung, and Blood Institute. Sep 2013-May 2018. #P01 HL69779.

Proteotoxicity: an underappreciated factor in cardiac disease. North American Coordinator. Leducq Transatlantic Alliance For Cardiovascular Disease. 2011-2016.

Marc E. Rothenberg, MD, PhD Director, Division of Allergy and Immunology 513-803-0257 marc.rothenberg@cchmc.org

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Marc E. Rothenberg, MD, PhD

Director, Division of Allergy and Immunology

Director, Cincinnati Center for Eosinophilic Disorders

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-0257

Fax 513-636-3310

Email marc.rothenberg@cchmc.org

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Clinical & Research Interests

Visit the Rothenberg Lab.

Clinical

Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy

Research

Eosinophils; chemokines

Biography

Visit the Rothenberg Lab website.

Dr. Rothenberg is director of the Division of Allergy and Immunology at Cincinnati Children's Hospital Medical Center and tenured professor of pediatrics at Cincinnati Children’s within the University of Cincinnati College of Medicine. He graduated summa cum laude with highest honors in chemistry and biochemistry from Brandeis University. He then completed the MD/PhD program at Harvard Medical School under Dr. Frank Austen, conducting studies on eosinophil hematopoiesis, as he developed the first culture system for human eosinophils. After completing residency at Children’s Hospital, Boston, Dr. Rothenberg did a fellowship in allergy/immunology and hematology at Children’s Hospital. Dr. Rothenberg did post-doctorate training with Dr. Philip Leder, Harvard Medical School, where he cloned the eotaxin chemokine. After being faculty at Harvard Medical School for one year, he came to the University of Cincinnati and Cincinnati Children's, where he has helped build a top program in research, and his division is a leader in allergy and immunology.

His research is focused on molecular analysis of allergic inflammation, primarily on the molecular pathogenesis of eosinophilic esophagitis. His laboratory takes a multi-disciplinary approach including the development of preclinical murine models: genetics, genomics, molecular immunology, and biochemistry. Dr. Rothenberg’s awards include the 2007 E Mead Johnson Award from the Society of Pediatric Research, 2010 National Institutes of Health MERIT Award, and being elected an American Association for the Advancement of Science fellow. He is a member of the American Society for Clinical Investigation, American Academy of Pediatrics, and Society for Pediatric Radiology. His publications number over 300. He has served on review panels for journals/grant agencies including National Institutes of Health (NIH), Burroughs Trust, and Medical Research Council of the United Kingdom. He served for four years on the Advisory Council of National Institute of Allergy and Infectious Disease. He has been associate editor of the Journal of Allergy and Clinical Immunology since 2004. His research has been supported by sources including the NIH, Human Frontier Science Program Organization, Burroughs Wellcome Fund, Dana Foundation, and Department of Defense.

MD, PhD: Harvard Medical School, Cambridge, MA, 1990.

Residency: Pediatrics, Children's Hospital, Boston, MA, 1991-1992.

Fellowship: Immunology / Allergy, Children's Hospital, Boston, MA, 1992-1994; Hematology / Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, MA, 1992-1995.

Certification: National Board of Medical Examiners, 1991; Board of Registration in Medicine, MA, 1992; American Board of Pediatrics, 1995, 2001, 2008; Ohio State Medical Board, 1997; American Board of Allergy and Immunology, 1997, 2006.

Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014 Aug;147(2):324:33.e5.

Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM, Kemme KA, Costello MS, Mingler MK, Blanchard C, Collins MH, Abonia JP, Putnam PE, Dellon ES, Orlando RC, Hogan SP, Rothenberg ME. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014 May;7(3):718-29.

Wen T, Stucke EM, Grotjan TM, Kemme KA, Abonia JP, Putnam PE, Franciosi JP, Garza JM, Kaul A, King EC, Collins MH, Kushner JP, Rothenberg ME. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology. 2013 Dec;145(6):1289-99.

Wen T, Besse JA, Mingler MK, Fulkerson PC, Rothenberg ME. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6067-72.

Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, Franciosi JP, Putnam PE, Eby M, Martin LJ, Aronow BJ, Rothenberg ME. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012 Apr;129(4):1064-75.e9.

Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, Gober L, Kim C, Glessner J, Frackelton E, Thomas K, Blanchard C, Liacouras C, Verma R, Aceves S, Collins MH, Brown-Whitehorn T, Putnam PE, Franciosi JP, Chiavacci RM, Grant SF, Abonia JP, Sleiman PM, Hakonarson H. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010 Apr;42(4):289-91.

Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HEC Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28.

Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa'ad AH, Putnam PE, Aronow BJ, Rothenberg ME. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006 Feb;116(2):536-47.

Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, Foster PS, Rothenberg ME. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001 Apr;2(4):353-60.

Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001 Jan;107(1):83-90.

Grants

NICHHD Pediatric Center for Gene Expression and Developmental Sciences. Training Director. National Institutes of Health. Dec 2011–Nov 2016. K12 HD028827.

Epithelial Genes in Allergic Inflammation. Co-Investigator. National Institutes of Health. Sep 2011–Aug 2016. U19 AI070235.

Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant Ulcerative Colitis. Co-Investigator. National Institutes of Health. Apr 2012–Mar 2016. R01 DK090119-01A1.

The Expression and Function of Paired Immunoglobulin-like Receptor B in Eosinophils. Co-Principal Investigator. U.S. - Israel Binational Science Foundation. Oct 2012–Sep 2016. #201144.

Arnold W. Strauss, MD Associate Director for External Relations and Strategic Projects, Cincinnati Children's Research Foundation 513-636-2942 arnold.strauss@cchmc.org

Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute 513-803-2790 jeffrey.whitsett@cchmc.org

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Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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Specialties

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.