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个人简介

Dr. David Josephy's research interests are in the field of Molecular Toxicology, including the development and application of bacterial mutagenicity assays, and mechanistic studies of enzymes that catalyze the metabolism of drugs and toxicants. Dr. Josephy teaches courses in Biochemistry, Molecular Biology, and Toxicology. He has advised more than two dozen graduate students and published more than 100 refereed papers. He is the co-author of the textbook "Molecular Toxicology" (Oxford University Press); the second edition was published in 2006. Josephy is also the Editor of the journal "Mutation Research - Genetic Toxicology and Environmental Mutagenesis" (Elsevier). Education B.Sc. Toronto Ph.D. University of British Columbia

研究领域

My research program focuses on enzymes of xenobiotic metabolism, especially the enzymes catalyzing glutathione conjugation and the processing of glutathione conjugates into mercapturic acids. We want to understand their mechanisms of catalytic activity and substrate specificity. We purify enzymes from both native sources and recombinant expression systems. We are characterizing the functional effects of SNPs (single-nucleotide polymorphisms) in the genes encoding these enzymes. We are also developing small-molecule inhibitors with possible therapeutic applications, including enhancement of the effectiveness of oncolytic viruses. 

近期论文

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Josephy, P.D., and Novak, M., Reactive electrophilic metabolites of aromatic amine and amide carcinogens, Frontiers in Bioscience 5: 341-359, 2013. Poon, J.C., and Josephy, P.D., Hydrolysis of S-aryl-cysteinylglycine conjugates catalyzed by porcine kidney cortex membrane dipeptidase, Xenobiotica 42: 1178-1186, 2012. Josephy, P.D., Pan, D., Ianni, M.D., and Mannervik, B. Functional studies of single-nucleotide polymorphic variants of human glutathione transferase T1-1 involving residues in the dimer interface, Archives of Biochemistry and Biophysics 513: 87-93, 2011. Josephy, P.D., Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology, Human Genomics and Proteomics 876940, 2010. Josephy, P.D., Kent, M., Mannervik, B., Single-nucleotide polymorphic variants of human glutathione transferase T1-1 differ in stability and functional properties, Archives of Biochemistry and Biophysics 490: 24-29, 2009.

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