Center Affiliation and Expertise: Systemic and Redox Toxicology
Dr. Duffel’s current research activities are centered on enzyme-catalyzed reactions that occur with xenobiotics. The major component of this effort includes studies to better understand and predict the role that sulfotransferases play in the cytotoxic, immunologic, mutagenic and carcinogenic responses to drugs, environmental chemicals, and other xenobiotics. This exploration of sulfotransferases employs a broad array of techniques in enzymology, biological chemistry, and chemistry that range from laboratory-based to computational approaches. These studies include investigations into the molecular bases for the substrate specificities, catalytic mechanisms, stereospecificities, and regulation of these enzymes. One major current research project, Aryl and Alcohol Sulfotransferases in Drug Metabolism, is funded by the National Cancer Institute. This project includes investigations on the role of sulfotransferases in a carcinogenic side-effect of a metabolite of the drug tamoxifen, studies on the mechanism and catalytic regulation of aryl and alcohol sulfotransferases, and development of methods to discover highly selective inhibitors of sulfotransferase isoforms. A second major research effort is directed towards understanding how polychlorinated biphenyls and their hydroxylated metabolites alter the regulation and catalytic function of the hydroxysteroid sulfotransferases. This is a component project, entitled PCBs and Hydroxysteroid (Alcohol) Sulfotransferases, within the Iowa Superfund Basic Research Program entitled Semi-volatile PCBs: Sources, Exposures, Toxicities. This research is funded by the National Institute of Environmental Health Sciences.