Yuan-Tsong Chen, M.D., Ph.D.

Professor of Pediatrics

Department:
Pediatrics

Division:
Medical Genetics

Email:
Chen0010mcdukeedu

Mailing Address:
Box 3028, DUMC
Durham, NC 27710

Telephone:
919-684-2036

Training:
M.D., Taiwan University Medical CollegePh.D., Columbia University College of Physicians and Surgeons

Last Updated:
October 01, 2009

Research Interests:
Our overall research interests are in translational research. We aim at translating the promise of genomic medicine into clinical reality.

Specific projects at present time include:

1). Identification of novel genes/targets associated with human diseases. This includes susceptibility genes for common multi-factorial diseases and adverse drug reactions. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics are some approaches that we use in identification of novel genes associated with the human disease. Genetic markers associated with drug-induced Stevens-Johnson syndrome and other adverse drug reactions have been identified. Prospective studies are in progress to assess the utilization of these markers to prevent the adverse drug reactions. A systematic, genome-wide, phenotype-driven mutagenesis program for gene function studies in the mouse have resulted in the identification of several mouse models of human genetic metabolic diseases. We will continue our research along these lines to identify more novel disease genes/ targets and to increase our understanding of the diseases.

2). Genetics and molecular mechanisms of Stevens-Johnson syndrome. With the identification of HLA-B allele strongly linked to the genetic susceptibility to the drug-induced Stevens-Johnson syndrome, we are investigating how the specific HLA allele mediated the cell toxicity in causing disseminated keratinocyte death.

3). Functional characterization of a novel glucose transporter and its role in diabetes mellitus. We cloned a novel glucose transporter (Glu 10), which is highly expressed in pancreas and liver and is located on a region of a chromosome where a diabetes mellitus type II locus has been mapped. We are currently investigating its role in diabetes by studying mouse models carrying the GLU10 mutations  and by direct genetic association study of human patients affected with diabetes.

4). Enzyme and gene therapy and targeting mechanisms of Pompe disease.
Pompe disease is a fatal genetic muscle disorder. As enzyme replacement therapy for Pompe disease moves into clinical reality the fundamental question of how the enzyme targets the heart and skeletal muscle and why some patients respond better than others remain unanswered. We have generated tissue-specific MPR300 knockout mouse model and other animal models to help answer these questions.

Publications:
2008 -- Wen MS, Lee MT, Chen JJ, Chuang HP, Lu LS, Chen CH, Lee TH, Kuo CT, Sun FM, Chang YJ, Kuan PL, Chen YF, Charng MJ, Ray CY, Wu JY, Chen YT. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.  Clin Pharmacol Ther, 84:83-9, 2008.

2007 -- Ou Yang CW, Hung SI, Juo CG, Lin YP, Fang WH, Lu IH, Chen ST, Chen YT. Human leukocyte antigen-B* 1502-bound peptides: Implication on the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.  J Allergy Clin Immun, 120:870-7, 2007.

2006 -- Kao H-J, Cheng C-F, Chen Y-H, Hung S-I, Huang C-C, Millington D, Kikuchi T, Wu J-Y, and Chen Y-T. ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein -subunit. Human Mol Genet, 15: 3569-3577, 2006.

2006 -- Hung SI, Chung WH Jee SH, Chen WC, Chang YT, Lee WR, Hu SL, Wu MT, Chen GS, Wong TW, Hsiao PF, Chen WH, Shih HY, Fan WH, Wei CY, Lou YH, Huang YL, Lin JJ, Chen YT. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenetics and Genomics, 16:297-306, 2006.

2006 -- Li LH, Ho SF, Chen CH, Wei CY, Li LY, Hung SI, Chung WH, Pan WH, Wong WC, Lee      MTM, Wu JY, Chen YT. Long contiguous stretches of homozygosity in the Human Genome, Human Mutation, 27:1115-21, 2006.

2005 -- Hung S-I, Chung W-H, Liou L-B, Chu C-C, Lin M, Huang H-P, Lin Y-L, Lan J-L, Yang L-C, Hong H-S, Chen M-J, Lai P-C, Wu M-S, Chu C-Y, Wang K-H, Chen C-H, Fann CSJ, Wu J-Y, Chen Y-T. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci, 102 (11): 4134-9,  2005.

2005 -- Yuan HY, Chen JJ, Lee MT Michel, Chen YF, Charng MJ, LU MJ, Hung CR, Wei CY, Chen CH, Wu YJ, Chen YT. A novel functional VKORC1 promoter polymorphysm is associated with inter-individual and inter-ethnic differences in wafarin sensitivity. Human Molecular Genetics, 14: 1745-1751, 2005.

2005 -- Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT: HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005, 102:4134-4139.

2004 -- Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT. A  marker for Stevens-Johnson syndrome. Nature, 248: 486, 2004.

2004 -- Wu JY, Kao HJ, Li SC, Stevens R, Hillman S, Millington D, Chen YT: ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. J Clin Invest 2004, 113:434-440.