Child Health Research Career Development Award

Dr. Aronow is a computational geneticist and developmental biologist. His group carries out analyses of many different kinds of data, develops algorithms, and builds websites and databases. These tools allow researchers from varying disciplines and backgrounds to analyze genetic and genomic data—either their own or that gathered from published sources—to better understand, model, and carry out new research about normal development and disease. His group is highly collaborative with clinical and basic researchers across a broad range of research projects encompassing many areas of biology and disease, including normal and abnormal development, in vivo and in vitro disease models, and large-scale clinical studies.

Data of interest includes genetic, genomic, proteomic, metabolomic, imaging, and therapeutic agent response measures. Recent areas of interest include large-scale clinical sample analyses, single cell-based dissection of developmental and disease tissues, and in vitro stem cell-based modeling of normal and disease-affected tissues including abnormal neurological, immunological, cardiac, and cancer tissues.

The lab’s recent efforts focus on predicting new therapeutic approaches based on disease mechanisms in the areas of inflammatory bowel disease, eosinophilic esophagitis, sickle cell anemia, cardiac development, and neurological and psychiatric diseases. His group is working on efforts to define the transcriptome of the developing kidney, lung and brain. They are using stem cell-derived cells and organoids to dissect mechanisms that underlie organ development and function as well as oncogenesis. They are also working to infer novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships.

Education and Training

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

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

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

Publications

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Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016 Aug 31;537(7622):698-702.

Bakeer N, James J, Roy S, Wansapura J, Shanmukhappa SK, Lorenz JN, Osinska H, Backer K, Huby AC, Shrestha A, Niss O, Fleck R, Quinn CT, Taylor MD, Purevjav E, Aronow BJ, Towbin JA, Malik P. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology. Proc Natl Acad Sci U S A. 2016 Aug30;113(35):E5182-91.

Kanisicak O, Khalil H, Ivey MJ, Karch J, Maliken BD, Correll RN, Brody MJ, J Lin SC, Aronow BJ, Tallquist MD, Molkentin JD. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun. 2016 Jul 22;7:12260.

Sarangdhar M, Tabar S, Schmidt C, Kushwaha A, Shah K, Dahlquist JE, Jegga AG, Aronow BJ. Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data. Nat Biotechnol. 2016 Jul 12;34(7):697-700.

Salomonis N, Dexheimer PJ, Omberg L, Schroll R, Bush S, Huo J, Schriml L, Ho Sui S, Keddache M, Mayhew C, Shanmukhappa SK, Wells J, Daily K, Hubler S, Wang Y, Zambidis E, Margolin A, Hide W, Hatzopoulos AK, Malik P, Cancelas JA, Aronow BJ, Lutzko C. Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium. Stem Cell Reports. 2016 Jul 12;7(1):110-25.

David I. Bernstein, MD, MA Director, Gamble Program and VTEU 513-636-7625 david.bernstein@cchmc.org

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David I. Bernstein, MD, MA

Director, Gamble Program and VTEU

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7625

Fax 513-636-7682

Email david.bernstein@cchmc.org

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Clinical & Research Interests

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Clinical

Rotavirus; herpes simplex virus; cytomegalovirus; preclinical and clinical evaluations of vaccine; immune response to herpes virus

Research

Evaluation of vaccines and antivirals for herpes and rotovirus; development of improved adjuvants and delivery systems for vaccines; treatment and prevention of influenza, norovirus and parvovirus infections

Biography

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Dr. Bernstein received his MA degree in microbiology and his MD degree from SUNY at Buffalo. His pediatric training was undertaken at USC and the New England Medical Center. This was followed by an ID fellowship at UCLA.

During his fellowship he became interested in herpes viruses and vaccines. Upon arrival at Cincinnati Children’s Hospital Medical Center he began his work investigating the immunobiology of genital herpes infections. At this time he also became interested in rotavirus and along with his colleague Dr. Richard Ward he investigated the immune responses that provide protection.

This work led to the development of a live attenuated human rotavirus vaccine initially named 89-12. The 89-12 vaccine was further modified and became the GlaxoSmithKline rotavirus vaccine, Rotarix, currently available in over 100 countries including the USA and EU. Dr. Bernstein is currently evaluating vaccines for CMV, HSV, influenza, avian influenza, RSV, norovirus and parvovirus. Dr. Bernstein has published over 200 manuscripts and book chapters on infectious diseases, vaccines and antivirals. Dr. Bernstein is currently the Albert Sabin Professor of pediatrics and director of the Division of Infectious Diseases at Cincinnati Children’s and directs one of eight NIH funded Vaccine Evaluation Units.

Education and Training

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MA: Microbiology, State University of New York at Buffalo, Buffalo, NY, 1973.

MD: State University of New York at Buffalo School of Medicine, Buffalo, NY, 1977.

Residency: Pediatrics, University of Southern California Medical Center, Los Angeles, CA; Tufts University School of Medicine, Boston, MA.

Fellowship: Pediatric Infectious Disease, University of California, Los Angeles, CA.

Certification: American Board of Medical Examiners, 1978; American Board of Pediatrics, 1981; Pediatrics, 1982.

Publications

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Staat MA, Rice MA, Donauer S, Payne DC, Bresee JS, Mast TC, Curns AT, Cortese MM, Connelly B, McNeal M, Ward RL, Bernstein DI, Parashar UD, Salisbury S. Estimating the rotavirus hospitalization disease burden and trends, using capture-recapture methods. Pediatr Infect Dis J. 2010 Dec;29(12):1083-6.

Widdice LE, Bernstein DI, Leonard AC, Marsolo KA, Kahn JA. Adherence to the HPV Vaccine Dosing Intervals and Factors Associated With Completion of 3 Doses. Pediatrics. 2010 Dec 13.

Bernstein DI, Epstein T, Murphy-Berendts K, Liss GM. Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes of the ACAAI and AAAAI collaborative study. Ann Allergy Asthma Immunol. 2010 Jun;104(6):530-5.

Sublett JW, Bernstein DI. Occupational rhinitis. Curr Allergy Asthma Rep. 2010 Mar;10(2):99-104.

Bernstein DI. The changing epidemiology of rotavirus gastroenteritis. Introduction. Pediatr Infect Dis J. 2009 Mar;28(3 Suppl):S49.

Bernstein DI, Cardin RD, Bravo FJ, Strasser JE, Farley N, Chalk C, Lay M, Fairman J. Potent adjuvant activity of cationic liposome-DNA complexes for genital herpes vaccines. Clin Vaccine Immunol. 2009 May;16(5):699-705.

Yee EL, Staat MA, Azimi P, Bernstein DI, Ward RL, Schubert C, Matson DO, Turcios-Ruiz RM, Parashar U, Widdowson MA, Glass RI. Burden of rotavirus disease among children visiting pediatric emergency departments in Cincinnati, Ohio, and Oakland, California, in 1999-2000. Pediatrics. 2008 Nov;122(5):971-7.

Bernstein DI, Edwards KM, Dekker CL, Belshe R, Talbot HK, Graham IL, Noah DL, He F, Hill H. Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults. J Infect Dis. 2008 Mar 1;197(5):667-75.

Bravo FJ, Cardin RD, Bernstein DI. A model of human cytomegalovirus infection in severe combined immunodeficient mice. Antiviral Res. 2007;76:104-110.

Kahn JA, Rosenthal SL, Tissot AM, Bernstein DI, Wetzel C, Zimet GD. Factors influencing pediatricians’ intention to recommend human papillomavirus vaccines. Ambul Pediatr. 2007;7:367-373.

Jorge A. Bezerra, MD Director, Division of Gastroenterology, Hepatology and Nutrition 513-636-3008 jorge.bezerra@cchmc.org

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Jorge A. Bezerra, MD

Director, Division of Gastroenterology, Hepatology and Nutrition

Medical Director, Pediatric Liver Care Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3008

Fax 513-636-5581

Email jorge.bezerra@cchmc.org

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Research Interests

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Visit the Bezerra Lab.

Biography

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Jorge A. Bezerra, MD, joined the Cincinnati Children's Hospital Medical Center Division of Gastroenterology, Hepatology and Nutrition in 1990, when he began his fellowship training in pediatric gastroenterology and nutrition and graduated in 1993.

From 1992-1994, Dr. Bezerra was a research scholar in the Division of Basic Sciences. He was appointed to the division in 1994 as an assistant professor within the UC Department of Pediatrics.

Dr. Bezerra completed his residency in pediatrics at the University of Arizona in Tucson, Arizona.

Dr. Bezerra has an active research career with his primary interests in molecular control of liver regeneration, biliary atresia, and genetic basis of intrahepatic cholestasis.

In addition to his research work, Dr. Bezerra is an active clinician for the outpatient GI clinical service and the inpatient liver service.

Education and Training

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MD: Federal University Rio Grande Norte, Natal, Brazil, 1984.

Residency: University of Arizona, Tuscon, AZ, 1989.

Fellowship: Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 1994.

Certification: Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition.

Publications

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View PubMed Publications

Bezerra JA. Biliary atresia in Brazil: where we are and where we are going. J Pediatr (Rio J). 2010 Nov-Dec;86(6):445-7.

Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee JC, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med. 2010 May 13;2(5):33.

Kumar Mohanty S, Ivantes CA, Mourya R, Pacheco C, Bezerra JA. Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis via Mip2/Cxcl2. Pediatr Res. 2010 Jan 6.

Shivakumar P, Sabla GE, Whitington P, Chougnet CA, Bezerra JA. Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia. J Clin Invest. 2009 Aug;119(8):2281-90.

Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem. 2009 May 8;284(19):12917-23.

Erickson N, Mohanty SK, Shivakumar P, Sabla G, Chakraborty R, Bezerra JA. Temporal-spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia. Hepatology. 2008 May;47(5):1567-77.

Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007 Jul;133(1):268-77.

Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, Bezerra JA. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26.

Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):99-103.

Shanmukhappa K, Sabla GE, Degen JL, Bezerra JA. Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor. BMC Gastroenterol. 2006 Nov 29;6:40.

Lee A. Denson, MD Medical Director, Inflammatory Bowel Disease Center 513-636-7575 lee.denson@cchmc.org

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Lee A. Denson, MD

Medical Director, Inflammatory Bowel Disease Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7575

Email lee.denson@cchmc.org

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Clinical & Research Interests

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Clinical

Inflammatory bowel disease; growth failure; celiac disease

Research

Visit the Denson Lab.

Biography

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The primary focus of Dr. Lee A. Denson's laboratory is to determine the molecular basis for alterations in growth hormone signaling in inflammatory bowel diseases (IBD).

Normal growth and development are dependent upon the ability of growth hormone to regulate IGF-1 expression. Evidence from studies in children with IBD and mouse models of colitis indicates that inflammatory cytokines which are up regulated in this setting may cause an acquired GH resistance. Consequences may include growth failure, altered body composition and impaired mucosal healing.

We are using complementary experimental and patient-based approaches to investigate regulation of growth hormone signaling in mouse models of colitis and in children with Crohn's disease. These include down regulation of the growth hormone receptor and up regulation of a family of post-receptor inhibitory proteins, the Suppressors of Cytokine Signaling (SOCS). These studies should lead to the development of more effective therapies for children with IBD and other chronic inflammatory conditions.

Education and Training

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MD: Medical College of Virginia, Richmond, VA, 1993.

Residency: Yale-New Haven Hospital, New Haven, CT, 1993-96.

Certification: Pediatrics, 1996 and 2002.

Fellowship: Yale University School of Medicine, New Haven, CT, 1996-99.

Publications

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View PubMed Publications

Ning K, Gettler K, Zhang W, Ng SM, Bowen BM, Hyams J, Stephens MC, Kugathasan S, Denson LA, Schadt EE, Hoffman GE, Cho JH. Improved integrative framework combining association data with gene expression features to prioritize Crohn's disease genes. Hum Mol Genet. 2015 Jul 15;24(14):4147-57.

Minar P, Haberman Y, Jurickova I, Wen T, Rothenberg ME, Kim MO, Saeed SA, Baldassano RN, Stephens M, Markowitz J, Rosh J, Crandall WV, Heyman MB, Mack DR, Griffiths AM, Baker SS, Hyams JS, Kugathasan S, Denson LA. Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. Inflamm Bowel Dis. 2014 Jun;20(6):1037-48.

Haberman Y, Tickle TL, Dexheimer PJ, Kim MO, Tang D, Karns R, Baldassano RN, Noe JD, Rosh J, Markowitz J, Heyman MB, Griffiths AM, Crandall WV, Mack DR, Baker SS, Huttenhower C, Keljo DJ, Hyams JS, Kugathasan S, Walters TD, Aronow B, Xavier RJ, Gevers D, Denson LA. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest. 2014 Aug;124(8):3617-33.

Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, González A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. The treatment-naïve microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014 Mar 12;15(3):382-92.

Dykes D, Towbin A, Bonkowski E, Chalk C, Bezold R, Lake K, Kim M, Heubi J, Trapnell B, Podberesky D, Denson L. Increased Prevalence of Luminal Narrowing and Stricturing by Enterography in Pediatric Crohn Disease Patients with Elevated Granulocyte-Macrophage Colony Stimulating Factor Auto-antibodies. Inflamm Bowel Dis. 2013 Sep;19(10):2146-54.

Jurickova I, Collins M, Chalk C, Seese A, Bezold R, Lake K, von Allmen D, Frischer J, Trapnell B, Denson L. Pediatric Crohn Disease Patients with Stricturing Behavior Exhibit Ileal Granulocyte-Macrophage Colony Stimulating Factor Auto-antibody Production and Reduced Neutrophil Bacterial Killing and GM-CSF Bioactivity. Clin Exp Immunol. 2013 Jun;172(3):455-65.

Samson CM, Jurickova I, Molden E, Schreiner W, Colliver J, Bonkowski E, Han X, Trapnell BC, Denson LA. Granulocyte-Macrophage Colony Stimulating Factor Blockade Promotes CCR9+ Lymphocyte Expansion in Nod2 Deficient Mice. Inflamm Bowel Dis. 2011 Dec;17(12):2443-55.

Han X, Uchida K, Jurickova I, Koch D, Willson T, Samson C, Bonkowski E, Trauernicht A, Kim MO, Tomer G, Dubinsky M, Plevy S, Kugathsan S, Trapnell BC, Denson LA. GM-CSF Auto-antibodies in Murine Ileitis and Progressive Ileal Crohn’s Disease. Gastroenterology. 2009 Apr;136(4):1261-71, e1-3.

Denson LA, Kim MO, Bezold R, Carey R, Osuntokun B, Nylund C, Willson T, Bonkowski E, Li D, Ballard E, Collins M, Moyer MS, Klein DJ. A randomized controlled trial of growth hormone in active pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2010 Aug;51(2):130-9.

Han X, Sosnowska D, Bonkowski E, Denson L. Growth hormone inhibits STAT3 activation and reduces disease activity in murine colitis. Gastroenterology. 2015;129:185-203.

Sudhansu K. Dey, PhD Lova Riekert Chair, Cancer and Cell Biology 513-803-1158 sk.dey@cchmc.org

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Sudhansu K. Dey, PhD

Lova Riekert Chair, Cancer and Cell Biology

Director, Division of Reproductive Sciences

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-1158

Fax 513-803-1160

Email sk.dey@cchmc.org

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Research Interests

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

Visit the Dey Lab.

Biography

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

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

Education and Training

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BSc: Presidency College, Calcutta, India, 1965.

MSc: University of Calcutta, India, 1967.

PhD: University of Calcutta, India, 1972.

Publications

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

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

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

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

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

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

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

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

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

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

John B. Harley, MD, PhD Director, Center for Autoimmune Genomics and Etiology (CAGE) 513-803-3665 john.harley@cchmc.org

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John B. Harley, MD, PhD

Director, Center for Autoimmune Genomics and Etiology (CAGE)

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-3665

Email john.harley@cchmc.org

Publications

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View PubMed Publications

Cobb BL, Fei Y, Jonsson R, Bolstad AI, Brun JG, Rischmueller M, Lester SE, Witte T, Illei G, Brennan M, Bowman S, Moser KL, Harley JB, Sawalha AH. Genetic association between methyl-CpG binding protein 2 (MECP2) and primary Sjögren’s syndrome. Ann Rheum Dis. 2010; 69(9): 1731-2.

Kim-Howard X, Maiti AK, Anaya J-M, Bruner GR, Brown E, Merrill JT, Edberg JC, Petri MA, Reveille JD, Ramsey-Goldman R, Alarcon GS, Vyse TJ, Gilkeson G, Kimberly RP, James JA, Guthridge JM, Harley JB, Nath SK. ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients with European ancestry. Ann Rheum Dis. 2010.

Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res. 2010; 20(2):170-179.

Harley JB, James JA. Everyone comes from somewhere: systemic lupus erythematosus and Epstein-Barr virus, induction of host interferon (INF) and humoral anti-EBNA1 immunity. Arthritis Rheum. 2010.

Bronson PG, Komorowski LK, Ramsay PP, May SL, Noble J, Lane JA, Thomson G, Claas FH, Seldin MF, Kelly JA, Harley JB, Moser KL, Gaffney PM, Behrens T, Criswell LA, Barcellos LF. Analysis of maternal-offspring HLA compatibility, parent-of-origin and noninherited effects for HLA-DRB1 in systemic lupus erythematosus. Arthritis Rheum. 2010.

Heinlen LD, McClain MT, Ritterhouse LL, Bruner BF, Edgerton CC, Keith MP, James JA, Harley JB. 60kD Ro and nRNP A frequently initiate human lupus autoimmunity. PLoS ONE. 2010 5(3):e9599.

Sammalisto S, Hiekkalinna T, Schwander K, Kardia S, Weder AB, Rodriquez BL, Doria A, Kelly JA, Bruner GR, Harley JB, Redline S, Larkin EK, Patel SR, Ewan AJ, Weber JL, Perola M, Peltonen L. Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex-and population-specific genetic effects. Eur J Hum Genet. 2009 Jan 1;17(2):258-266.

Poole BD, Templeton AK, Guthridge JM, Brown EJ, Harley JB, James JA. Aberrant Epstein-Barr viral infection in systemic lupus erythematosus. Autoimmun Rev. 2009 Feb;8(4):337-42.

Poole BD, Schneider RI, Guthridge JM, Velte CA, Reichlin M, Harley JB, James JA. Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus. Arthritis Rheum. 2009 Feb 26; 60(3):848-859.

Han S, Kim-Howard X, Deshmukh H, Kamatani Y, Viswanathan P, Guthridge JM, Thomas K, Kaufman KM, Ojwang J, Rojas-Villarraga A, Baca V, Orozco L, Rhodes B, Choi CB, Gregersen PK, Merrill JT, James JA, Gaffney PM, Moser KL, Jacob CO, Kimberly RP, Harley JB, Bae SC, Anaya JM, Alarcon-Riquelme ME, Matsuda K, Vyse TJ, Nath SK. Evaluation of imputation-based association in and around the Integrin-α-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Hum Mol Genet. 2009 Mar 15;18(6):1171-80.

Gurjit (Neeru) Khurana Hershey, MD, PhD Director, Division of Asthma Research 513-636-7054 gurjit.hershey@cchmc.org

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Gurjit (Neeru) Khurana Hershey, MD, PhD

Director, Division of Asthma Research

Co-Director, Office of Pediatric Clinical Fellowships

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7054

Fax 513-636-1657

Email gurjit.hershey@cchmc.org

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Clinical & Research Interests

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Clinical

Asthma; allergic rhinitis; food allergy; urticaria

Research

Genetics of allergy and asthma; cytokines; signaling pathways

Visit the Khurana Hershey Lab.

Biography

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Gurjit Khurana Hershey, MD, PhD, received a BS degree from the University of Iowa, and MD and PhD degrees from Washington University School of Medicine. After completing pediatric residency and an allergy/immunology fellowship at St. Louis Children’s Hospital, Dr. Khurana Hershey joined the faculty at Cincinnati Children’s Hospital Medical Center within the University of Cincinnati College of Medicine. She now directs the Division of Asthma Research at Cincinnati Children’s Hospital Medical Center and is the director of the Medical Scientist Training Program at the University of Cincinnati College of Medicine.

In addition to her clinical duties, Dr. Khurana Hershey directs an NIH-funded research program focused on the genetics and genomics of allergic inflammation with a focus on cytokines and signal transduction. Her research has been continuously funded for over fifteen years. She is the principal investigator of an NIH-funded Asthma and Allergic Diseases Cooperative Research Center (AADCRC), and is also the PI of the Inner City Asthma Consortium, an NIH funded subcontract. She is the PI of the UC T32 MSTP training grant. In addition to her research contributions, she is an outstanding clinician and teacher/mentor. Several of her trainees now hold academic faculty positions. She is the recipient of the 2013 Cincinnati Children’s Educational Achievement Award.

Dr. Khurana Hershey is a fellow of the American Pediatric Society and the American Academy of Allergy, Asthma and Immunology. She serves on the Executive Council of the American Academy of Asthma, Allergy and Immunology Program Committee, is the chair of the Grant Review Committee and appointed vice chair of the Basic and Immunology Interest Section. She is a member of the Editorial Board of the Journal of Allergy and Clinical Immunology. She was recently named One of the Five Leading Women in Healthcare in the Greater Cincinnati Metropolitan Area, and Outstanding Woman at Cincinnati Children’s Hospital Medical Center.

Education and Training

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BS: University of Iowa, Iowa City, IA, 1985.

PhD: Washington University School of Medicine, St. Louis, MO, 1990.

MD: Washington University School of Medicine, St. Louis, MO, 1992.

Residency: St. Louis Children's Hospital, St. Louis, MO, 1992-1995.

Fellowship: St. Louis Children's Hospital, St. Louis, MO, 1995-1997.

Board Certification: American Board of Pediatrics, 2009 - Present.

Board Certification: American Board of Allergy and Immunology, 2008 - Present.

Publications

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Biagini Myers JM, Martin LJ, Butsch Kovacic M, Mersha TB, He H, Pilipenko V, Lindsey MA, Ericksen MB, Bernstein DI, LeMasters GK, Lockey JE, Khurana Hershey GK. Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma. J Allergy Clin Immunol. 2014 May 13. pii: S0091-6749(14)00520-X.

Wood RA, Togias A, Wildfire J, Visness CM, Matsui EC, Gruchalla R, Hershey G, Liu AH, O’Connor GT, Pongracic JA, Zoratti E, Little F, Granada M, Kennedy S, Durham SR, Shamji MH, Busse WW. Development of cockroach immunotherapy by the Inner-City Asthma Consortium. J Allergy Clin Immunol. 2014 Mar;133(3)846-52.

Zhang Z, Xiao C, Gibson AM, Bass SA, Khurana Hershey GK. EGFR signaling blunts allergen-induced IL-6 production and Th17 responses in the skin and attenuates development and relapse of atopic dermatitis. J Immunol. 2014 Feb 1:192(3):859-66.

Kinker KG, Gibson AM, Bass SA, Day BP, Deng, J, Medvedovic M, Figueroa JA, Hershey GK, Chen W. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma. PloS One. 2014 Jan 10;9 (1):e85148.

Acciani TH, Brandt EB, Khurana Hershey GK, Le Cras TD. Diesel exhaust particle exposure increases severity of allergic asthma in young mice and children. Clin Exp Allergy. 2013 Dec;43(12):1406-18.

Brandt EB, Kovacic MB, Lee GB, Gibson AM, Acciani TH, Le Cras TD, Budelsky AL, Khurana Hershey GK. Diesel exhaust particle induction of IL17A contributes to severe asthma. J Allergy Clin Immunol. 2013 Nov:132(5);1194-1204.

Brandt EB, Gibson AM, Bass S, Khurana Hershey GK. Exacerbation of Allergen-Induced Eczema in TLR4- and TRIF-Deficient Mice. J Immunol. 2013 Oct 1;191(7):3519-25.

Chen W, Sivaprasad U, Gibson AM, Ericksen MB, Cunningham CM, Bass SA, Kinker KG, Finkelman FD, Wills-Karp M, Khurana Hershey GK. IL-13 receptor α2 contributes to development of experimental allergic asthma. J Allergy Clin Immunol. 2013 Oct;132(4):951-958.

Lee GB, Brandt EB, Xiao C, Gibson AM, Le Cras TD, Brown LA, Fitzpatrick AM, Khurana Hershey GK. Diesel exhaust particles induce cysteine oxidation and S-glutathionylation in house dust mite induced murine asthma. PLoS One. 2013;8(3):e60632.

Mintz-Cole RA, Brandt EB, Bass SA, Gibson AM, Reponen T, Khurana Hershey GK. Surface availability of beta-glucans is critical determinant of host immune response to C. cladosporioides J Allergy Clin Immunol. 2013 Jul;132(1):159-69.

James E. Heubi, MD Director, Center for Clinical and Translational Science and Training 513-636-9776 sandra.geideman@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 513-636-9776

Fax 513-803-1039

Email sandra.geideman@cchmc.org

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Clinical & Research Interests

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Clinical

Pediatric gastroenterology; hepatology and nutrition; pediatric cholestatic liver disease

Research

Pediatric cholestatic liver disease; childhood bone disease; fat malabsorption

Biography

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James Heubi, MD, is associate dean for clinical and translational research and professor of pediatrics at the University of Cincinnati College of Medicine. He is the director of the Center for Clinical and Translational Science and Training which is the vehicle by which the University of Cincinnati, Cincinnati Children’s Hospital Medical Center and the Veterans Administration Medical Center administer the NIH-funded, Clinical Translational Science Award and director of the Division of Gastroenterology, Hepatology and Nutrition at the Cincinnati Children’s Hospital Medical Center.

He has been an active clinical investigator with over 195 peer reviewed publications and was the long term program director for the NIH funded General Clinical Research Center. He is the principal investigator and co-investigator on NIH grants and participates is a local principal or co-investigator on two rare disease networks supported by the NIH.

His research interests include cholestatic liver disease in childhood and its complications, inborn errors of bile acid metabolism, bone disease in gastrointestinal and hepatobiliary disorders, fat absorption, and cholesterol absorption and metabolism.

Education and Training

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

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

Fellowship: Pediatric Gastroenterology, Children's Hospital Medical Center, Cincinnati, OH, 1979.

Certification: Pediatric Gastroenterology and Nutrition, 1990.

Publications

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Heubi JE, Setchell KDR, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2015 Jan;61(1):268-274.

Setchell KDR, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O’Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013 May;144(5):945-955.

Gonzales E, Gerhardt MF, Fabre M, Setchell KDR, Davit-Spraul A, Vincent I, Heubi JE, Bernard O, Jacquemin E. Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy. Gastroenterology. 2009 Oct;137(4):1310-1320.

Setchell KDR, Heubi JE, Bove KE, O’Connell NC, Brewsaugh T, Steinberg SJ, Moser A, Squires Jr RH. Liver disease caused by failure to racemize trihydroxycholestanocic acid: gene mutation and effect of bile acid therapy. Gastroenterology. 2003 Jan;124(1):217-232.

Oelkers P, Kirby LC, Heubi JE, Dawson PA. Primary bile acid malabsorption caused by mutations in the ileal sodi¬um-de¬pen¬dent bile acid transporter gene (SLC10A2). J Clin Invest. 1997 Apr 15;99(8):1880-1887.

Heubi JE, Hollis BW, Specker B, Tsang RC. Bone disease in chronic childhood cholestasis I. Vitamin D absorption and metabolism. Hepatology. 1989 Feb;9(2):258-264.

Setchell KDR, Suchy FJ, Welsh MB, Zimmer-Nechemias L, Heubi JE, Balistreri WF. Δ4-3-Oxosteroid 5B-reductase deficiency described in identical twins with neonatal hepatitis - A new inborn error in bile acid synthesis. J Clin Invest. 1988 Dec; 82(6):2148-2157.

Heubi JE, Daugherty CC, Partin JS, Partin JC, Schubert WK. Grade l Reye's Syndrome--outcome and predictors of progression to deeper coma grades. N Engl J Med. 1984 Dec 13;311(24):l539-1554.

Lichtenstein PK, Heubi JE, Daugherty CC, Farrell MK, Sokol RJ, Rothbaum RJ, Suchy FJ, Balistreri WF. Grade l Reye's Syndrome. A frequent cause of vomiting and liver dysfunction following varicella and upper respiratory tract infection. N Engl J Med. 1983 Jul;309(3):l33-139.

Heubi JE, Balistreri WF, Fondacaro JD, Partin JC, Schubert WK. Primary bile acid malabsorption: Defective in vitro ileal active bile acid transport. Gastroenterology. 1982 Oct;83(4):804-8ll.

Grants

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Cincinnati Center for Clinical and Translational Science and Training. Principal Investigator. National Center for Advancing Translational Sciences/National Institutes of Health. Aug 2015-Mar 2019. UL1 TR000077-05.

Pediatric Gastroenterology and Nutrition Training Grant. Mentor. National Institute of Diabetes and Digestive and Kidney Diseases/ National Institutes of Health. Jul 2005-Jun 2020. T32 DK007727.

Clinical Center of Cholestatic Liver Disease in Children (CHILDREN). Co-Investigator. National Institute of Diabetes and Digestive and Kidney Diseases/ National Institutes of Health. Sep 2009-May 2019. U01 DK062497.

Sterol and Isoprenoid Diseases Consortium. Site Principal Investigator. Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health. Sep 2009-Jul 2019. U54 HD061939.

Bone Mineral Accretion in Young Children. Co-Investigator. Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health. Sep 2013-Jul 2018. R01 HD076321.

Short Term Medical Student Training Grant. Principal Investigator. National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Apr 2002-Mar 2019. T35 DK060444-11.

Margaret K. Hostetter, MD BK Rachford Professor and Chair, Department of Pediatrics 513-636-4509 margaret.hostetter@cchmc.org

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

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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

Biography

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Dr. Jobe is a neonatologist and professor of pediatrics at Cincinnati Children’s. His research contributions include studies of surfactant metabolism, the hormonal regulation of lung maturation, mechanisms of lung injury with mechanical ventilation, and neonatal resuscitation. He has been chair of the NICHD Neonatal Research Network Steering Committee and chair of the NICHD Global Research Network Steering Committee. He has a 26-year collaborative research project on fetal development with Professor John Newnham at the University of Western Australia. He remains actively involved with clinical and translational research to improve outcomes for infants. He was an associate editor for Journal of Pediatrics for 18 years. He presently is a consultant for the Bill and Melinda Gates Foundation for infant mortality. Noteworthy recognitions are the E. Mead Johnson Award for Pediatric Research, the Virginia Apgar Award from the AAP, and election to The US National Institute of Medicine.

Education and Training

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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.

Publications

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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.

Raphael Kopan, PhD Director, Division of Developmental Biology 513-636-1299

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Raphael Kopan, PhD

Director, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1299

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Research Interests

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

Visit the Kopan Lab.

Biography

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

Education and Training

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

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

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

Publications

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

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

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

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

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

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

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

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

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

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

Richard A. Lang, PhD Director, Visual Systems Group 513-636-2700 richard.lang@cchmc.org

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Richard A. Lang, PhD

Director, Visual Systems Group

Academic Affiliations

Professor, UC Department of Pediatrics

UC Department of Ophthalmology

Phone 513-636-2700

Fax 513-803-0740

Email richard.lang@cchmc.org

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Research Interests

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

Visit the Lang Lab.

Education and Training

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

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

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

Publications

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

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

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

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

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

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

Timothy D. LeCras, PhD Associate Director of Admissions, Medical Scientist Training Program 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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Research Interests

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Lung development; bronchopulmonary dysplasia; pulmonary hypertension; asthma; pulmonary fibrosis

Biography

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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.

Education and Training

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Postdoctoral fellow: University of Virginia, Charlottesville, VA, 1993-1996.

PhD: University of Cambridge, UK, 1988-1992.

BSc: Biochemistry, Brunel University, London, UK, 1983-1987.

Publications

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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.

Jeffery D. Molkentin, PhD Professor | Howard Hughes Medical Institute Investigator 513-636-3557 jeff.molkentin@cchmc.org

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

Director, Division of Human Genetics

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-7902

Email louis.muglia@cchmc.org

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Specialties

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Pediatric endocrinology

Visit the Muglia Lab.

Biography

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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.

Education and Training

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

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

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

Publications

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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

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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.

S. Steven Potter, PhD 513-636-4850 steve.potter@cchmc.org

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S. Steven Potter, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4850

Fax 513-636-4317

Email steve.potter@cchmc.org

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Research Interests

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

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Education and Training

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

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

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

Publications

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View PubMed Publications

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

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

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

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

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

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

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

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

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

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

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

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

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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

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Biography

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Jeff Robbins CV (.pdf)

Publications

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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

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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

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Clinical

Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy

Research

Eosinophils; chemokines

Visit the Rothenberg Lab.

Biography

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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.

Visit the Rothenberg Lab website.

Education and Training

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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.

Publications

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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
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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.

Harinder Singh, PhD Director, Division of Immunobiology 513-636-7641 harinder.singh@cchmc.org

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Harinder Singh, PhD

Director, Division of Immunobiology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7641

Email harinder.singh@cchmc.org

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

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Arnold W. Strauss, MD

Associate Director for External Relations and Strategic Projects, Cincinnati Children's Research Foundation

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-2942

Email arnold.strauss@cchmc.org

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Clinical Interests
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Pediatric cardiology; genetic basis of pediatric heart disease; General Cardiology Outpatient Clinic

Biography
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Arnold Strauss, MD, joined Cincinnati Children's in April, 2007, as chairman of the Department of Pediatrics at the UC College of Medicine, chief medical officer of Cincinnati Children's and director of the Cincinnati Children's Research Foundation. He is the seventh B.K. Rachford Memorial Chair in Pediatrics.

Dr. Strauss is a distinguished pediatric cardiologist, scientist, educator and leader. Prior to his arrival at Cincinnati Children's, he was the chairman of the Department of Pediatrics at the Vanderbilt University School of Medicine and medical director of the Monroe Carell Jr. Children's Hospital at Vanderbilt, a position he held from 2000 to 2007. Under his leadership, the university built and opened a new hospital for children, expanded its pediatric faculty and increased grant funding for pediatric research. From 1981 to 2000, Strauss was director of the Division of Pediatric Cardiology at Washington University/St. Louis Children's Hospital.

A respected scientist, Dr. Strauss' research focuses on understanding the molecular basis of disorders of mitochondrial fatty acid oxidation and the genetic causes of congenital heart disease and cardiomyopathies. He is the recipient of two of the most prestigious awards in research. In November 2006 he was awarded the American Heart Association's Basic Science Research Award for groundbreaking work that led to finding genetic defects that can cause heart failure and sudden death in infants and children. In 1991 he received the E. Mead Johnson Award for Excellence in Pediatric Research.

Education and Training
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MD: Washington University, St. Louis, MO, 1970.

Residency: Pediatrics, Children's Hospital, St. Louis, MO, 1970-72.

Fellowship: Cardiology, Children's Hospital and Washington University, St. Louis, MO, 1972-75.

Postdoctoral Fellowship: Merck, Sharp and Dohme Research Laboratories, Rahway, NJ, 1975-77.

Publications
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View PubMed Publications

Liebig M, Schymik I, Mueller M, Wendel U, Mayatepek E, Ruiter J, Strauss AW, Wanders RJ, Spiekerkoetter U. (2006) Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels. Pediatrics. 118:1065-9.

Khuchua Z, Yue Z, Batts L, Strauss AW. (2006) A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function. Circ Res. 99:201-8.

Exil VJ, Gardner CD, Rottman JN, Sims H, Bartelds B, Khuchua Z, Sindhal R, Ni G, Strauss AW. (2006) Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase. Am J Physiol Heart Circ Physiol. 290:H1289-97.

Bennett MJ, Russell LK, Tokunaga C, Narayan SB, Tan L, Seegmiller A, Boriack RL, Strauss AW. (2006) Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase. Mol Genet Metab. 89:74-9.

Strauss AW. (2005) Surprising? Perhaps not. Long-chain fatty acid oxidation during human fetal development.  Pediatr Res. 57:753-4.

Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Ijlst L, Vaz FM, van Vlies N, Overmars H, Duran M, Wijburg FA, Wanders RJ, Strauss AW. (2005) Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice. Pediatr Res. 57:760-4.

Shekhawat PS, Matern D, Strauss AW. (2005) Fetal fatty acid oxidation disorders, their effect on maternal health and neonatal outcome: impact of expanded newborn screening on their diagnosis and management. Pediatr Res. 57:78R-86R.

Djouadi F, Aubey F, Schlemmer D, Ruiter JP, Wanders RJ, Strauss AW, Bastin J. (2005) Bezafibrate increases very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders. Hum Mol Genet. 14:2695-703.

Browning MF, Larson C, Strauss A, Marsden DL. (2005) Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects. J Inherit Metab Dis. 28:545-50.

Strauss AW. (2004) Tandem mass spectrometry in discovery of disorders of the metabolome. J Clin Invest. 113:354-6.

Spierkerkoetter U, Khuchua Z, Yue Z, Strauss AW. (2004) The early-onset phenotype of mitochondrial trifunctional protein deficiency: a lethal disorder with multiple tissue involvement.  J Inherit Metab Dis. 27:294-6.

Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Exil V, Duran M, Wijburg FA, Wanders RJ, Strauss AW. (2004) Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress.  Eur J Clin Invest. 34:191-6.

Spiekerkoetter U, Khuchua Z, Yue Z, Bennett MJ, Strauss AW. (2004) General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover. Pediatr Res. 55:190-6.

Spiekerkoetter U, Bennett MJ, Ben-Zeev B, Strauss AW, Tein I. (2004) Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional protein. Muscle Nerve. 29:66-72.

McKinney JT, Longo N, Hahn SH, Matern D, Rinaldo P, Strauss AW, Dobrowolski SF. (2004) Rapid, comprehensive screening of the human medium chain acyl-CoA dehydrogenase gene. Mol Genet Metab. 82:112-20.

Strauss A, Lock JE. (2003) Pediatric cardiomyopathy--a long way to go. N Engl J Med. 348:1703-5.

Spiekerkoetter U, Sun B, Zytkovicz T, Wanders R, Strauss AW, Wendel U. (2003) MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency. J Pediatr. 143:335-42.

Spiekerkoetter U, Sun B, Khuchua Z, Bennett MJ, Strauss AW. (2003) Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.  Hum Mutat. 21:598-607.

Shekhawat P, Bennett MJ, Sadovsky Y, Nelson DM, Rakheja D, Strauss AW. (2003) Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases. Am J Physiol Endocrinol Metab. 284:E1098-105.

Khuchua Z, Wozniak DF, Bardgett ME, Yue Z, McDonald M, Boero J, Hartman RE, Sims H, Strauss AW. (2003) Deletion of the N-terminus of murine map2 by gene targeting disrupts hippocampal ca1 neuron architecture and alters contextual memory.  Neuroscience. 119:101-11.

Exil VJ, Roberts RL, Sims H, McLaughlin JE, Malkin RA, Gardner CD, Ni G, Rottman JN, Strauss AW. (2003) Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice. Circ Res. 93:448-55.

Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, Strauss AW, Comeau AM, Eaton RB, Grady GF. (2001) Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem. 47:1945-55.

Ibdah JA, Paul H, Zhao Y, Binford S, Salleng K, Cline M, Matern D, Bennett MJ, Rinaldo P, Strauss AW. (2001) Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. J Clin Invest. 107:1403-9.

Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ. (2000) Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase. J Biol Chem. 275:27186-96.

Ibdah JA, Bennett MJ, Rinaldo P, Zhao Y, Gibson B, Sims HF, Strauss AW. (1999) A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.  N Engl J Med. 340:1723-31.

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

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Clinical & Research Interests
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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
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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.

Education and Training
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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.

Publications
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View PubMed Publications

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.

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.

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.

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.

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.

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

Education and Training
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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.

Publications
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View PubMed Publications

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

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

High Res

Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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

Visit the Whitsett Lab.

Biography
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Dr. Whitsett's laboratory discovered surfactant proteins B and C, cloned the genes encoding the surfactant proteins A, B, C, and D, Scgb1a1, TTF-1 and others and utilized transgenic mouse models to delete and mutate these genes in transgenic mice. They identified transcriptional networks regulating lung morphogenesis and perinatal lung maturation contributing to the understanding of the roles of TTF-1, CEBPα, SOX2, SOX17, FOXA1, FOXA2, FOXA3, SPDEF, KLF5, CDC42 and others using both in vitro and in vivo methods. They identified multiple transcription factors regulating goblet cell differentiation airway epithelial cells including critical role of SPDEF, FOXA3 and airway goblet cells controlling innate immunity. They produced transgenic mouse models for conditional deletion and expression of genes involved in lung development, disease, and repair. They have generated transgenic models of pulmonary adenocarcinoma and explored the role of transcription factors mediating pulmonary adenocarcinoma in vivo and in vitro. They utilized RNA-Seq, microarray, Chip-Seq in the application of Nex-Gen sequencing and bioinformatics to identify and understand networks involved in the regulation of lung development and disease using clinical sample, as well as in vitro and in vivo models.

Dr. Whitsett has a long interest in training both in the clinical setting in “Neonatology” and in “Pulmonary Biology” and has contributed to the direct training of more than 80 graduate or post-graduate students in his laboratory. The scope of his work is represented in several recent reviews. Initial discoveries from his laboratory provided early insights into the genes and proteins critical for surfactant function including ABCA3, SFTPC, SFTPB, SFTPA, SFTPD.

Education and Training
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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.

Publications
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Davies ER, Kelly JFC, Howarth PH, Wilson DI, Holgate ST, Davies DE, Whitsett JA, Haitchi HM. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life. JCI Insight. 2016;1:e87632.

Ustiyan V, Zhang Y, Perl A-KT, Whitsett JA, Kalin TV, Kalinichenko VV. ß-Catenin and Kras/Foxm1 Signaling Pathway are Critical to Restrict Sox9 in Basal Cells During Pulmonary Branching Morphogenesis. Dev Dyn. 2016;245:590-604.

Guo M, Wang H, Potter SS, Whitsett JA, Xu Y. SINCERA: A pipeline for single-cell RNA-Seq profiling analysis. PLoS Comput Biol. 2015;11:e1004575.

Kamath-Rayne BD, Du Y, Hughes M, Wagner EA, 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;8:67.

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;70:1092-1094.

Snowball J, Ambalavanan M, Whitsett J, Sinner D. Endodermal Wnt signaling is required for tracheal cartilage formation. Dev Biol. 2015;405:56-70.

Wakata K, Tsuchiya T, Tomoshige K, Takagi K, Yamasaki N, Matsumoto K, Miyazaki T, Nanashima A, Whitsett JA, Maeda Y, Nagayasu T. A favorable prognostic marker for EGFR mutant non-small cell lung cancer: immunohistochemical analysis of MUC5B. BMJ Open. 2015;5:e008366.

Ishida N, Fukazawa T, Maeda Y, Yamatsuji T, Kato K, Matsumoto K, Shimo T, Takigawa N, Whitsett JA, Naomoto Y. A novel P13K inhibitor iMDK suppresses non-small cell lung Cancer cooperatively with a MEK inhibitor. Exp Cell Res. 2015;335:197-206.

Rajavelu P, Chen G, Xu Y, Kitzmiller JA, Korfhagen TR, Whitsett JA. Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation. J Clin Invest. 2015;125:2021-2031.

Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J, Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Dev Biol. 2015;401:264-275.

Grants
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Airway Progenitor Cell Proliferation and Differentiation During Lung Repair. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Jan 2012-Dec 2016. U01HL110964.

Transcriptional Programming of Asthma Related Pathology in Respiratory Epithelia. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2013-Mar 2018. 2 R01HL095580.

Omics of Lung Diseases. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2013-May 2018. K12 HL119686.

“Lung Map” Atlas Research Center. Multiple Principal Investigators. National Institutes Health/National Heart, Lung, and Blood Institute. Jun 2014-Apr 2019. U01 HL122642.

Editing Alveolar Progenitor Cells for Correction of Monogenic Disease. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2016-Aug 2023. U01 HL134745.

Role of EMC3/TMEM111 in Alveolar Epithelial Cell Function. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2017-Mar 2022. R01 HL136722.

Hector R. Wong, MD Director, Division of Critical Care Medicine 513-636-4259 hector.wong@cchmc.org

High Res

Hector R. Wong, MD

Director, Division of Critical Care Medicine

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4259

Fax 513-636-4267

Email hector.wong@cchmc.org

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Specialties
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Critical care; sepsis
Visit the Wong Lab.

Education and Training
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MD: University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, 1989.

Residency: Department of Pediatrics, George Washington University School of Medicine, Children's National Medical Center, Washington, DC, 1990 to 1992.

Fellowship: Clinical Fellow, Department of Anesthesiology, Division of Pediatric Critical Care Medicine, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, 1992 to 1995; Research Fellow, Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 1992 to 1995.

Certification: National Board of Medical Examiners, 1990; Diplomate, American Board of Pediatrics, 1993; American Board of Pediatrics: Sub-Board of Pediatric Critical Care Medicine, 1996.

Publications
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View PubMed Publications

Solan PD, Dunsmore KE, Denenberg AG, Odoms K, Zingarelli B, Wong HR. A novel role for matrix metalloproeinase-8 in sepsis. Crit Care Med. . 2011.

Wong HR, Wheeler DS, Tegtmeyer K, Poynter SE, Kaplan JM, Chima RS, Stalets E, Basu RK, Doughty LA. Toward a clinically feasible gene expression-based subclassification strategy for septic shock: proof of concept. Crit Care Med. 2010 Oct;38(10):1955-61.

Wong HR, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Willson DF, Freishtat RJ, Anas N, Meyer K, Checchia PA, Monaco M, Odom K, Shanley TP. Identification of pediatric septic shock subclasses based on genome-wide expression profiling. BMC Med. 2009 Jul 22;7:34.

Wong HR, Cvijanovich N, Allen GL, Lin R, Anas N, Meyer K, Freishtat RJ, Monaco M, Odoms K, Sakthivel B, Shanley TP; Genomics of Pediatric SIRS/Septic Shock Investigators. Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum. Crit Care Med. 2009 May;37(5):1558-66.

Wong HR, Cvijanovich N, Wheeler DS, Bigham MT, Monaco M, Odoms K, Macias WL, Williams MD. Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock. Am J Respir Crit Care Med. 2008 Aug 1;178(3):276-82.

Cvijanovich N, Shanley TP, Lin R, Allen GL, Thomas NJ, Checchia P, Anas N, Freishtat RJ, Monaco M, Odoms K, Sakthivel B, Wong HR; Genomics of Pediatric SIRS/Septic Shock Investigators. Validating the genomic signature of pediatric septic shock. Physiol Genomics. 2008 Jun 12;34(1):127-34.

Shanley TP, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, Kalyanaraman M, Tofil NM, Penfil S, Monaco M, Odoms K, Barnes M, Sakthivel B, Aronow BJ, Wong HR. Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock. Mol Med. 2007 Sep-Oct;13(9-10):495-508.

Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, Kalyanaraman M, Tofil NM, Penfil S, Monaco M, Tagavilla MA, Odoms K, Dunsmore K, Barnes M, Aronow BJ; Genomics of Pediatric SIRS/Septic Shock Investigators. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007 Jul 18;30(2):146-55.

Aneja R, Odoms K, Dunsmore K, Shanley TP, Wong HR. Extracellular heat shock protein-70 induces endotoxin tolerance in THP-1 cells. J Immunol. 2006 Nov 15;177(10):7184-92.

Wong HR, Ryan M, Wispé JR. Stress response decreases NF-kB nuclear translocation and increases I-kBα expression in A549 cells. J Clin Invest. 1997;99:2423-2428.

Yi Zheng, PhD Director, Experimental Hematology and Cancer Biology 513-636-0595 yi.zheng@cchmc.org

High Res

Yi Zheng, PhD

Director, Experimental Hematology and Cancer Biology

Institute Co-Director, Cancer and Blood Diseases Institute

Katherine Stewart Waters Endowed Chair

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-0595

Fax 513-636-3768

Email yi.zheng@cchmc.org

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Research Interests
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Using transgenic and gene targeted mouse models to study the physiological and pathological roles of Rho GTPases and their regulators in hematopoiesis, neurogenesis, lung cancer development and small intestinal stem cell regulations mechanism based, rational design of small molecule inhibitors targeting Rho GTPase signaling modules and pathologic functions in cancer and blood diseases; mouse model studies of mTor signaling function in hematopoietic stem cells and small intestinal stem cells.

Visit the Zheng Lab.

Education and Training
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BS: Tsinghua University, Beijing, China, 1986.

MS: Cornell University, Ithaca, NY, 1988.

PhD: Cornell University, Ithaca, NY, 1991.

Postdoctoral Fellow: Cornell University, Ithaca, NY, 1995.

Publications
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View All PubMed Publications

Kesarwani M, Huber E, Kincaid Z, Evelyn CR, Biesiada J, Rance M, Thapa MB, Shah NP, Meller J, Zheng Y, Azam M. Targeting substrate-site in Jak2 kinase prevents emergence of genetic resistance. Sci Report. 2015. In press.

Konstantinidis DG, Giger KM, Risinger M, Pushkaran S, Zhou P, Dexheimer P, Yerneni S, Andreassen P, Klingmüller U, Palis J, Zheng Y, Kalfa TA. Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation. Blood. 2015 Jul 30. [Epub ahead of print]

Barry DM, Xu K, Meadows SM, Zheng Y, Norden PR, Davis GE, Cleaver O. Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation. Development. 2015 Aug 7. [Epub ahead of print]

Yang JQ, Kalim KW, Li Y, Zhang S, Hinge A, Filippi MD, Zheng Y, Guo F. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. 2015 Jun 19. [Epub ahead of print]

Lin Y, Zheng Y. Approaches for targeting Rho GTPases in cancer drug discovery. Expert Opin Drug Discov. 2015 Sep;10(9):991-1010.

Zandvakili I, Davis AK, Hu G, Zheng Y. Loss of RhoA exacerbates, rather than dampens, oncogenic K-Ras induced lung adenoma formation in mice. PLoS One. 2015 Jun 1;10(6):e0127923.

Evelyn CR, Biesiada J, Duan X, Tang H, Shang X, Nelson S, Seibel WL, Meller J, Zheng Y. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme. J Biol Chem. 2015 May 15;290(20):12879-98.

Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams RH, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat Commun. 2015 Apr 10;6:6725.

Li J, Zhang L, Chen Z, Xie M, Huang L, Xue J, Liu Y, Liu N, Guo F, Zheng Y, Kong J, Zhang L. Cocaine activates Rac1 to control structural and behavioral plasticity in caudate putamen. Neurobiol Dis. 2015 Mar;75:159-76.

Chang KH, Nayak RC, Roy S, Perumbeti A, Wellendorf AM, Bezold KY, Pirman M, Hill SE, Starnes J, Loberg A, Zhou X, Inagami T, Zheng Y, Malik P, Cancelas JA. Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation. Nat Commun. 2015 Jan 9;6:5914.

Grants
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Targeting Cdc42 for bone marrow transplant therapies. Principal investigator. National Institutes of Health. Apr 2015 - Apr 2020. NIH R01CA193350.

Cdc42, hematopoietic stem cell polarity and cell fate. Principal Investigator. National Institute of Health - NIDDK. Dec 2015 - Nov 2019.

Blood stem cell aging and biomarker studies. Co-Principal Investigator. National Institute of Health - NHLBI. Aug 2016 - July 2020.

Activated protein C peptides for radio-mitigation. Co-Principal Investigator. National Institute of Health - NIAID. Apr 2017 - Mar 2019.

Leukemia Stem cell polarity and differentiation therapy. Co-Principal Investigator. National Institute of Health - NCI. Sep 2017 - July 2022.

Basilia Zingarelli, MD, PhD Director, Basic Science Research 513-636-8704 basilia.zingarelli@cchmc.org

High Res

Basilia Zingarelli, MD, PhD

Director, Basic Science Research

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8704

Email basilia.zingarelli@cchmc.org

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Specialties
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Sepsis; trauma; hemorrhagic shock and ischemia and reperfusion injury.
Visit the Zingarelli Lab.

Biography
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Basilia Zingarelli, MD, PhD, came to Cincinnati Children's Hospital Medical Center in 1995 as a post-doctoral research fellow in Critical Care Medicine. She joined the faculty of the University of Cincinnati College of Medicine in 1997.

Dr. Zingarelli graduated from the Medical School of the University of Messina in Italy in 1990. She also obtained a doctorate in experimental medicine in 1997 and attended a residency in medical toxicology at the University of Messina from 1990 to 1992.

Dr. Zingarelli now directs the basic science research in the Division of Critical Care Medicine. She directs an NIH-funded research laboratory focused on the pathogenetic mechanisms of organ injury during sepsis, trauma and hemorrhage and coordinates basic science and clinical translational research projects related to other critical care conditions.

Dr. Zingarelli serves on the Executive Council of the Shock Society, a well-established international association of clinical and research scientists in the field of shock and trauma, and serves as associate editor for the journal Shock. She also serves as permanent and ad hoc member on a number of study sections at the National Institutes of Health.

Education and Training
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MD: School of Medicine, University of Messina, Italy, 1990.

PhD: Experimental Medicine, School of Medicine, University of Messina, Italy, 1997.

Residency: Medical Toxicology, School of Medicine, University of Messina, Italy, 1990-1992.

Certification: General Medicine (Italian), 1990.

Publications
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View PubMed Publications

Chima RS, LaMontagne T, Piraino G, Hake PW, Denenberg A, Zingarelli B. C-peptide, a novel inhibitor of lung inflammation following hemorrhagic shock. Am J Physiol Lung Cell Mol Physiol. 2011 May;300(5):L730-9.

Solan PD, Piraino G, Hake PW, Denenberg A, O'Connor M, Lentsch A, Zingarelli B. Liver X receptor α activation with the synthetic ligand T0901317 reduces lung injury and inflammation after hemorrhage and resuscitation via inhibition of the NF-κB pathway. Shock. 2011; 35:367-374.

Kaplan JM, Hake PW, Denenberg A, Nowell M, Piraino G, Zingarelli B. Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 Is associated with the downregulation of peroxisome proliferator-activated receptor (PPAR)-γ during polymicrobial sepsis. Mol Med. 2010 Nov-Dec;16(11-12):491-7.

Zingarelli B, Piraino G, Hake PW, O'Connor M, Denenberg A, Fan H, Cook JA. Peroxisome proliferator-activated receptor {delta} regulates inflammation via NF-{kappa}B signaling in polymicrobial sepsis. Am J Pathol. 2010 Oct;177(4):1834-47.

Zingarelli B, Chima R, O'Connor M, Piraino G, Denenberg A, Hake PW. Liver apoptosis is age dependent and is reduced by activation of peroxisome proliferator-activated receptor-gamma in hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol. 2010 Jan;298(1):G133-41.

Kaplan JM, Denenberg A, Monaco M, Nowell M, Wong H, Zingarelli B. Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock. Intensive Care Med. 2010 Jan;36(1):123-30.

Zingarelli B, Hake PW, O'Connor M, Burroughs TJ, Wong HR, Solomkin JS, Lentsch AB. Lung injury after hemorrhage is age dependent: role of peroxisome proliferator-activated receptor gamma. Crit Care Med. 2009 Jun;37(6):1978-87.

Zingarelli B, Fan H, Ashton S, Piraino G, Mangeshkar P, Cook JA. Peroxisome proliferation-activated receptor (PPAR) γ is not necessary for the development of LPS-induced tolerance. Immunology, 2008;124:51-57.

Chima RS, Hake PW, Piraino G, Mangeshkar P, Denenberg A, Zingarelli B. Ciglitazone ameliorates lung inflammation by modulating the inhibitor kappaB protein kinase/nuclear factor-kappaB pathway after hemorrhagic shock. Crit Care Med. 2008 Oct;36(10):2849-57.

Vish MG, Mangeshkar P, Piraino G, Denenberg A, Hake PW, O'Connor M, Zingarelli B. Proinsulin c-peptide exerts beneficial effects in endotoxic shock in mice. Crit Care Med. 2007 May;35(5):1348-55.

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