A major goal of our lab is to understand the role of genetic polymorphism in human susceptibility to environmental diseases and response to therapeutic drugs. We have been focused our research activities on the functional characterization of genetic variants of human cytochrome P450 2A6 (CYP2A6) and of human O 6 -alkylguanine DNA-alkyltransferase (AGT). CYP2A6 is responsible for the metabolism of nicotine, gasoline ethers and tobacco-specific carcinogens such as 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK). AGT is critical in repairing DNA damage induced by alkylating agents. Functional characterization of polymorphic variants of CYP2A6 and AGT will provide essential information for molecular epidemiology studies to assess their roles in individual susceptibility to relevant environmental toxins. With the aid of computer modeling, we have also studied the mechanisms of activity loss of some CYP2A6 polymorphic variants, such as the Leu160His and Gly479Val variants, and the structure/activity relationship of CYP2A6 and CYP2A13. In collaboration with the EOHSI Analytical Center, our laboratory has established a new LC/MS method for determination of the metabolites of carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and used it to study the metabolism of PhIP in human prostate tissue.

	Identification of critical amino acid residues of human CYP2A13 for the metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-specific carcinogen. He XY, Shen J, Ding X, Lu AY, Hong JY. Drug Metab Dispos. 2004 Aug; 32(12): Epub ahead of print
	Genetic polymorphisms of CYP2E1, GSTT1, GSTP1, GSTM1, ALDH2, and ODC and the risk of advanced precancerous gastric lesions in a Chinese population. You W, Hong JY, Zhang L, Pan K, Pee D, Li J, Ma J, Rothman N, Caporaso N, Fraumeni JF, Xu G, Gail MH. Cancer Epidemiol Biomarkers Prev. 2004; in press
	Identification of Val117 and Arg372 as critical amino acid residues for the activity difference between human CYP2A6 and CYP2A13 in coumarin 7-hydroxylation. He XY, Shen J, Hu WY, Ding X, Lu AY, Hong JY. Arch Biochem Biophys. 2004 Jul 15;427(2):143-53.
	Metabolic and biochemical issues in the molecular epidemiology of cancer. Snyder R, Hong JY. IARC Sci Publ. 2004;(157):51-69.