Bruce D Gelb, MD
- Professor, Pediatrics (Cardiology)
Professor, Genetics and Genomic Sciences
Director, Child Health and Development Institute
Director, Center for Molecular Cardiology
Specialties:Pediatrics, Pediatric Cardiology
Research Topics:Cardiovascular, Gene Discovery, Human Genetics and Genetic Disorders, Signal Transduction, Stem Cells, Transgenic Mice
Dr. Bruce D. Gelb is the Gogel Family Chair and Director of The Mindich Child Health and Development Institute, Director of the Center for Molecular Cardiology, and Professor of Pediatrics and Genetics and Genomic Sciences. He is board certified in Pediatric Cardiology by the American Board of Pediatrics.
In his quest to discover what causes congenital heart disease, Dr. Gelb has developed an extensive program in genomics and gene investigation, focusing on traits associated with heart malformations.
An expert in Noonan syndrome, Dr. Gelb has studied the genetic origins of this disease to understand its pathogenesis. Noonan and related syndromes result from mutations in several genes that encode proteins that cells use to signal from the outer membrane to the nucleus. Dr. Gelb and colleagues examine whether stem cells generated from cultured skin cells malfunction, leading to developmental disorders, and whether it is possible to coax cellular development to function normally.
At The Mindich Child Health and Development Institute, Dr. Gelb has created a collaborative multidisciplinary research environment to advance translational research into prevalent diseases of childhood. The emphasis is on the application of genetics and genomics toward elucidating the causes of illness affecting infants, children, and adolescents. To maximize resources and the impact of investigation, four centers of research areas were initially identified: Allergy and Asthma, Cardiovascular Defects, Neurodevelopmental Disorders, and Obesity and Diabetes; more recently, the MCHDI has expanded its focus to include broader topics in children’s health.
Dr. Gelb is a distinguished recipient of the E. Mead Johnson Award from the Society for Pediatric Research and the Norman J. Siegel New Member Outstanding Science Award from the American Pediatric Society. He was elected to the National Academy of Medicine and the American Society of Clinical Investigation. In addition to his research, Dr. Gelb directs the Cardiovascular Genetics Program at Mount Sinai. He is the current President of the International Pediatric Research Foundation and a council member of the American Pediatric Society. After earning a medical degree from the University of Rochester Medical School in Rochester, New York, Dr. Gelb completed a pediatric residency and a pediatric cardiology fellowship at Babies Hospital of Columbia-Presbyterian Medical Center and Texas Children's Hospital at the Baylor College of Medicine, respectively. He joined the faculty at Mount Sinai in 1991.
Areas of Expertise
Cardiovascular Genetics, Heart Transplantation
Multi-Disciplinary Training AreasBiophysics and Systems Pharmacology [BSP], Genetics and Genomic Sciences [GGS]
MD, Univ. of Rochester Sch. Med. & Den.
Residency, Pediatrics, Columbia-Presbyterian Medical Ctr.
Fellowship, Pediatric Cardiology, Texas Children's Hospital
Specific Clinical/Research Interests:
Genetics of congenital heart defects; Noonan syndrome and related disorders; Gain-of-function RAS signaling
Genetic Counselor: Meghan Mac Neal
Postdoctoral Fellows: Amy Kontorovich, Se-Yeon Lee
Predoctoral Students: Katie Landy, Felix Richter, Nelson Rodriguez, Carolyn Sommer
Research Personnel: Adolfo Aleman, Céline Guichard, Angelika Nitzl, Jian Zhang
Summary of Research Studies:
The Gelb research group is focused on disease gene discovery using genomic techniques and characterization of the biological roles of such genes in disease pathogenesis. The focus of the laboratory currently is on those traits that are associated with heart malformations. In the past, we have identified disease genes for Char and Noonan syndromes. The former is TFAP2B, which encodes a transcription factor of the AP-2 family, and the latter include PTPN11, KRAS, SOS1, SOS2, RAF1 and SHOC2. We are studying the roles of these disease genes in normal developmental and homeostatic processes as well as in disease pathogenesis. We are actively studying additional human genetic traits, both simple and complex, to identify additional disease genes with a particular focus on traits with cardiovascular abnormalities. This is being done with next generation sequencing approaches, both whole exome and genome sequencing. Ongoing biologic studies focus on disease modeling using induced pluripotent stem cells, including creating mutations or correcting them with CRISPR technology. We are also studying disease genes and performing drug discovery in Drosophila melanogaster.
- The Congenital Heart Disease Genetic Network Study (CHD GENES)
The goal of this study is to obtain a DNA sample and clinical information from individuals with congenital heart disease and their families in order to better understand the genetics of congenital heart disease.
- RASopathy registry for individuals with a diagnosis of a RASopathy and hypertrophic cardiomyopathy
The goal of this study is to observe and track disease progression in people with hypertrophic cardiomyopathy (HCM) due to a RASopathy syndrome.
McKean DM, Homsy J, Wakimoto H, Patel N, Gorham J, DePalma SR, Ware JS, Zaidi S, Ma W, Patel N, Lifton RP, Chung WK, Kim R, Shen Y, Brueckner M, Goldmuntz E, Sharp AJ, Seidman CE, Gelb BD, Seidman JG. Loss of RNA expression and allele-specific expression associated with congenital heart disease. Nature communications 2016 Sep; 7.
Josowitz R, Mulero-Navarro S, Rodriguez NA, Falce C, Cohen N, Ullian EM, Weiss LA, Rauen KA, Sobie EA, Gelb BD. Autonomous and Non-autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes. Stem cell reports 2016 Aug;.
Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE, Karczewski KJ, DePalma SR, McKean D, Wakimoto H, Gorham J, Jin SC, Deanfield J, Giardini A, Porter GA, Kim R, Bilguvar K, López-Giráldez F, Tikhonova I, Mane S, Romano-Adesman A, Qi H, Vardarajan B, Ma L, Daly M, Roberts AE, Russell MW, Mital S, Newburger JW, Gaynor JW, Breitbart RE, Iossifov I, Ronemus M, Sanders SJ, Kaltman JR, Seidman JG, Brueckner M, Gelb BD, Goldmuntz E, Lifton RP, Seidman CE, Chung WK. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science (New York, N.Y.) 2015 Dec; 350(6265).
Mulero-Navarro S, Sevilla A, Roman AC, Lee DF, D'Souza SL, Pardo S, Riess I, Su J, Cohen N, Schaniel C, Rodriguez NA, Baccarini A, Brown BD, Cavé H, Caye A, Strullu M, Yalcin S, Park CY, Dhandapany PS, Yongchao G, Edelmann L, Bahieg S, Raynal P, Flex E, Tartaglia M, Moore KA, Lemischka IR, Gelb BD. Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia. Cell reports 2015 Oct;.
Glessner JT, Bick AG, Ito K, Homsy JG, Rodriguez-Murillo L, Fromer M, Mazaika E, Vardarajan B, Italia M, Leipzig J, DePalma SR, Golhar R, Sanders SJ, Yamrom B, Ronemus M, Iossifov I, Willsey AJ, State MW, Kaltman JR, White PS, Shen Y, Warburton D, Brueckner M, Seidman C, Goldmuntz E, Gelb BD, Lifton R, Seidman J, Hakonarson H, Chung WK. Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data. Circulation research 2014 Oct; 115(10).
Edwards JJ, Martinelli S, Pannone L, Lo IF, Shi L, Edelmann L, Tartaglia M, Luk HM, Gelb BD. A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype. American journal of medical genetics. Part A 2014 Sep; 164A(9).
Josowitz R, Lu J, Falce C, D'Souza SL, Wu M, Cohen N, Dubois NC, Zhao Y, Sobie EA, Fishman GI, Gelb BD. Identification and purification of human induced pluripotent stem cell-derived atrial-like cardiomyocytes based on sarcolipin expression. PloS one 2014 Jul; 9(7).
Dhandapany PS, Razzaque MA, Muthusami U, Kunnoth S, Edwards JJ, Mulero-Navarro S, Riess I, Pardo S, Sheng J, Rani DS, Rani B, Govindaraj P, Flex E, Yokota T, Furutani M, Nishizawa T, Nakanishi T, Robbins J, Limongelli G, Hajjar RJ, Lebeche D, Bahl A, Khullar M, Rathinavel A, Sadler KC, Tartaglia M, Matsuoka R, Thangaraj K, Gelb BD. RAF1 mutations in childhood-onset dilated cardiomyopathy. Nature genetics 2014 Jun; 46(6).
Carey AS, Liang L, Edwards J, Brandt T, Mei H, Sharp AJ, Hsu DT, Newburger JW, Ohye RG, Chung WK, Russell MW, Rosenfeld JA, Shaffer LG, Parides MK, Edelmann L, Gelb BD. Effect of copy number variants on outcomes for infants with single ventricle heart defects. Circulation. Cardiovascular genetics 2013 Oct; 6(5).
Zaidi S, Choi M, Wakimoto H, Ma L, Jiang J, Overton JD, Romano-Adesman A, Bjornson RD, Breitbart RE, Brown KK, Carriero NJ, Cheung YH, Deanfield J, DePalma S, Fakhro KA, Glessner J, Hakonarson H, Italia MJ, Kaltman JR, Kaski J, Kim R, Kline JK, Lee T, Leipzig J, Lopez A, Mane SM, Mitchell LE, Newburger JW, Parfenov M, Pe'er I, Porter G, Roberts AE, Sachidanandam R, Sanders SJ, Seiden HS, State MW, Subramanian S, Tikhonova IR, Wang W, Warburton D, White PS, Williams IA, Zhao H, Seidman JG, Brueckner M, Chung WK, Gelb BD, Goldmuntz E, Seidman CE, Lifton RP. De novo mutations in histone-modifying genes in congenital heart disease. Nature 2013 Jun; 498(7453).
Carvajal-Vergara X, Sevilla A, D'Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 2010 Jun; 465(7299).