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Research UW Affiliations and Teaching Responsibility Former Postdocs and Graduate Students
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Research
Metabolic basis of conjugated diene toxicity; biochemical and molecular
characterization of flavin-containing monooxygenases; biochemical mechanisms of
nephrotoxicity; synthesis and evaluation of kidney-selective prodrugs of anticancer
agents. Current research focuses on the biochemical mechanisms of toxicity of
three important industrial chemicals, 1,3-butadiene, styrene, and trichloroethylene, which
are also released into the environment and have been associated with carcinogenicity,
hepatotoxicity, and nephrotoxicity. Modern chemical, biochemical, and toxicological techniques are used to
investigate the mechanisms of toxicity. For example, the enzymes involved in bioactivation
and detoxication of these chemicals are isolated and characterized, to determine if
expression of these enzymes in different tissues, and/or species is an important
determinant of species, gender, tissue and/or age-related differences in toxicity. In
addition, toxicant-derived reactive metabolite adducts with blood protein and DNA are
characterized to develop sensitive biomarkers for exposure. The knowledge gained regarding the biochemical basis of tissue
selectivity of various toxicants is also used in this laboratory to design and develop new
therapeutic agents that would have greater tissue selectivity and less systemic toxicity
than existing drugs. |