EHSRC Investigator Detail
| Michael W. Duffel | |
| Professor of Pharmacy |
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| Email: michael-duffel@uiowa.edu | |
| Phone: (319) 335-8840 | |
| EHSRC Role(s): | Member, Oxidative Stress and Metabolism Research Cluster |
Research Interests
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.
Recent Publications
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Liu Y, Apak TI, Lehmler HJ, Robertson LW, Duffel MW. Hydroxylated polychlorinated biphenyls are substrates and inhibitors of human hydroxysteroid sulfotransferase SULT2A1. Chem Res Toxicol. 2006 Nov;19(11):1420-5. PMID: 17112228 [PubMed - indexed for MEDLINE]
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Sharma V, Duffel MW. A comparative molecular field analysis-based approach to prediction of sulfotransferase catalytic specificity. Methods Enzymol. 2005;400:249-63. PMID: 16399353 [PubMed - indexed for MEDLINE]
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Kim SY, Laxmi YR, Suzuki N, Ogura K, Watabe T, Duffel MW, Shibutani S. Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha-hydroxytamoxifen in rat and human livers. Drug Metab Dispos. 2005 Nov;33(11):1673-8. Epub 2005 Aug 11. PMID: 16099924 [PubMed - indexed for MEDLINE]
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Apak TI, Duffel MW. Interactions of the stereoisomers of alpha-hydroxytamoxifen with human hydroxysteroid sulfotransferase SULT2A1 and rat hydroxysteroid sulfotransferase STa. Drug Metab Dispos. 2004 Dec;32(12):1501-8. Epub 2004 Sep 15. PMID: 15371299 [PubMed - indexed for MEDLINE]
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Sheng JJ, Saxena A, Duffel MW. Influence of phenylalanines 77 and 138 on the stereospecificity of aryl sulfotransferase IV. Drug Metab Dispos. 2004 May;32(5):559-65. PMID: 15100179 [PubMed - indexed for MEDLINE]