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Wendy K. Chung, M.D., Ph.D.
Assistant Professor of Pediatrics
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Research
Summary
Dr. Wendy Chung is a human geneticist whose current research activities include efforts to identify genes and their relevant allelic variants related to the development of congenital diaphragmatic hernia, congenital cardiac malformations including heterotaxy, hypoplastic left heart syndrome, cardiac septal defects, cardiomyopathies, and congenital and acquired long QT syndromes. In genetic studies of arrhythmias, the patient’s personal history of inciting triggers, T wave morphology on ECG, and the family history are used to choose candidate genes for linkage analysis when possible and mutation identification in one of the genes/loci identified to date in long QT syndrome. In genetic studies of hypertrophic cardiomyopathy, the patient’s history of age of onset, other associated medical problems, and family history are used to choose candidate genes for mutation identification. In studies of congenital heart disease and congenital diaphragmatic hernias, the probands are studied by comparative genomic hybridization to detect genomic alterations such as insertions or deletions on a genome wide basis. Then candidate genes are selected based upon their roles in embryonic diaphragmatic and cardiac development and screened for mutations by high throughput sequencing. Genotype-phenotype correlations are then made by comparing clinical features and outcome based on genetic etiology of a disease.
Another area of research includes the identification of genes related to obesity and type 2 diabetes in mice and humans. Dr. Chung and associates have mapped and cloned naturally occurring spontaneous mutations in the mouse causing both monogenic forms of obesity (tubby and diabetes) as well as a suppressor of obesity called mahoganoid. We have also identified 25 quantitative trait loci (QTLs) that interact with monogenic forms of obesity to produce varying degrees of diabetes susceptibility. We have made congenic lines for most of these QTLs and have identified a QTL for diabetes call Lisch-like. In parallel with these rodent studies, Dr. Chung is a participant in large ongoing human genetic studies to identify the genetic susceptibility to obesity and diabetes in humans. In collaboration with investigators around the world, we have access to over 100,000 human subjects phenotyped for adiposity and have developed high throughput methods for sequencing large genomic regions for regulatory variants and have identified novel contiguous gene deletions associated with syndromic forms of obesity. We are also studying the molecular mechanism by which the genes FTO/FTM recently identified through large genome wide association studies cause increased adiposity. We have identified novel mutations in the Wolframin gene causing a rare autosomal recessive form of diabetes mellitus and characterized the uniparental disomy of chromosome 6 in neonates with transient neonatal diabetes. In addition, families with maturity onset diabetes of the young (MODY) and have identified a rare neonatal complication of hypoglycemia associated with MODY.
Dr. Chung also provide the molecular genetics core services for the Obesity Research Center, Diabetes and Endocrine Research Center, Pediatric Neuromuscular Clinical Research Network studying spinal muscular atrophy, and the Pediatric Heart Network.
http://nbdiabetes.org/about/about/wendy.html
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Selected Publications:
1. Bankston, JR, Yue, M, Chung, W, Spyres, M, Pass, R, Silver, E, Sampson, KJ, Kass, RS. (2007) A Novel and Lethal de Novo LQT-3 Mutation in a Newborn with a Distinct Molecular Pharmacology and Therapeutic Response: Implications for Mutation-Specific Therapy in Infants. PLoS One.
2(12):e1258
2. Kaufman, BD, Auerbach, S, Reddy, S, Manlhiot, D, Deng, L, Prakash, A, Printz, BF, Gruber, D, Papavassiliou, S, Hsu, S, Sehnert, A, Chung, WK. (2007) Mital, S. RAAS Gene Polymorphisms Influence Progression of Pediatric Hypertrophic Cardiomyopathy. Human Genetics
122(5):515-523
3. Jean, A, Mansukhani, M, Oberfield, SE, Fennoy, I, Nakamoto, J, Atwan, M, Lerer, I, Ben Neriah, Z, Zangen, DH, Chung, WK. (2008) Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Estriol Amniotic Fluid Analysis and Molecular Genetic Testing. Prenatal Diagnosis.
28(1):11-14
4. Gordon, E, Panaghie, P, Deng, L, Bee, KJ, Ostrer, H, Basson, CT, Chung, WK, Abbott, GW. (2008) A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovascular Research
77(1):98-106
5. Stratigopoulos, G, Padilla, S, LeDuc, C, Watson, E, Hattersley, A, McCarthy, M, Chung, W, Leibel, R. (2008) Regulation of Fto/Ftm gene expression in mice and humans. Am. J. Physiology- Regulatory, Integrative & Comparative Physiology
294(4):R1185-1196
6. Dokmanovic-Chouinard, M, Chung, WK, Chevre, JC, Yonan, J, Wiegand, B, Bromberg, Y, Wakae, N, Watson, E, Wright, C, Overton, J, Ito, R, LeDuc, C, Solomon, K, Fischer, SG, Leibel, RL. (2008) Positional Cloning of “Lisch-like”, a Candidate Modifier of Susceptibility to Type 2 Diabetes in Mice. PLoS Genetics
:In Press
7. Chung, WK, Patki, A, Matsuoka, N, Boyer, BB, Liu, N, Musani, SK, Goropashnaya, A, Tan, PL, Katsanis, N, Johnson, SB, Gregersen, PK, Allison, DB, Leibel, RL, Tiwari, HK. (2008) Analysis of 30 genes (355 SNPS) related to energy homeostasis for association with adiposity in European-American and Yup’ik Eskimo populations. Human Heredity
:Accepted.
8. Dimos, JT, Rodolfa, KT, Niakan, KN, Weisenthal, LN, Mitsumoto, H, Chung, W, Croft, GF, Saphier, G, Leibel, R, Goland, R, Wichterle, H, Henderson, CE, Eggan, K. (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science
:Accepted.
9. Bankston, JR, Sampson, KJ, Sateriy, S, Glaaser, IW, Malito, DL, Chung, WK, Kass, RS. (2008) A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences. Channels
:Accepted
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