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MIKI 2008

Michael W. Duffel

Tel.  (319)-335-8840
Email:  michael-duffel@uiowa.edu

Education
  • B.S., Chemistry, University of Texas at Austin, 1975

  • Ph.D., Chemistry (Biochemistry), University of Texas at Austin, 1979

    Duffel Research Presentation
Professional Experience
National Institutes of Health, Enzyme and Cellular Biochemistry Section, Laboratory of Biochemistry and Metabolism, NIDDK, Staff Fellow, 1979-1981
University of Iowa, College of Pharmacy, Assistant Professor, 1981-1986
University of Iowa, College of Pharmacy, Associate Professor, 1986-1993
University of Iowa, College of Pharmacy, Professor, 1993-present
University of Iowa, College of Pharmacy, Professor and Associate Dean for Graduate Education and Research, 1995-present
Research
Dr. Duffel's research interests concern the biochemistry of enzymes involved in mammalian conversion of drugs to reactive metabolites that mediate toxic and therapeutic effects. His current research includes studies on the specificity, mechanisms, and regulation of sulfotrans-ferases that are involved in drug metabolism and chemical carcinogenesis.
Representative Publications

 Liu, Y., Apak, T.I., Lehmler, H.-J., Robertson, L.W., and Duffel, M.W. 2006. Hydroxylated polychlorinated biphenyls are substrates and inhibitors of human hydroxysteroid sulfotransferase SULT2A1.  Chemical Research in Toxicology, 19:1420-1425.

Sharma, V. and Duffel, M.W. 2005. A comparative molecular field analysis (CoMFA) based approach to prediction of sulfotransferase catalytic specificity. Methods in Enzymology, 400:  249-263.
Kim, S.Y., Laxmi, Y.R., Suzuki, N., Ogura, K., Watabe, T., Duffel, M.W., and Shibutani, S.  2005.  Formation of Tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of a-hydroxytamoxifen in rat and human livers.  Drug Metabolism and Disposition, 33:1673-1678.
Sheng, J., Saxena, A., and Duffel, M.W. 2004.  Influence of phenylalanines 77 and 138 on the stereospecificity of aryl sulfotransferase IV.  Drug Metabolism and Disposition, 32: 559-565.
Apak, T. I. and Duffel, M.W. 2004. Interactions of the stereoisomers of a-hydroxytamoxifen with human hydroxysteroid sulfotransferase SULT2A1 and rat hydroxysteroid sulfotransferase STa. Drug Metabolism and Disposition, 32: 1501-1508.
Sheng, J. and Duffel, M.W. 2003. Enantioselectivity of human hydroxysteroid sulfotransferase ST2A3 with Naphthyl-1-ethanols. Drug Metabolism and Dispostion, 31: 697-700
Sharma, V. and Duffel, M.W. 2002. Homology model-based Comparative Molecular Field Analysis of the substrate specificity of an aryl sulfotransferase. Journal of Medicinal Chemistry, 45: 5514-5522
Sheng, J. and Duffel, M.W. 2001. Bacterial expression, purification, and characterization of rat hydroxysteroid sulfotransferase STa. Protein Expression and Purification, 21:235-242.
Sheng, J., Sharma, V., and Duffel, M.W. 2001. Measurement of aryl and alcohol sulfotransferase activity. Current Protocols in Toxicology, 4.5.1 - 4.5.9.
Shibutani, S., Ravinderath, A., Terashima, I., Suzuki, N., Laxmi, Y.R.S., Kanno, Y, Suzuki, M., Apak, T.I., Sheng, J., and Duffel, M.W. 2001. Mechanism of lower genotoxicity of toremifene compared with tamoxifen. Cancer Research, 61:3925-3931.
Duffel, M.W., Marshall, A.D., McPhie, P., Sharma, V., and Jakoby, W.B. 2001. Enzymatic aspects of the phenol (aryl) sulfotransferases. Drug Metabolism Reviews, 33: 369-395.
Deshpande, G., Schoenwald, R.D., Barfknecht, C.F., and Duffel, M.W. 2000. In vitro and ex vivo hydrolysis rates of ethacrynate esters and their relationship to intraocular pressure in the rabbit eye. Journal of Ocular Pharmacology and Therapeutics, 16:539-556.
King, R.S., Sharma, V., Pedersen, L.C., Kakuta, Y., Negishi, M., and Duffel, M.W. 2000. Structure-function modeling of the interactions of N-alkyl-N-hydroxyanilines with rat hepatic aryl sulfotransferase IV, Chemical Research in Toxicology, 13:1251-1258.
Banoglu, E. and Duffel, M.W. 1999. Importance of peri-interactions on the stereospecificity of hydroxysteroid sulfotransferase STa with 1-arylethanols. Chemical Research in Toxicology, 12:278-285.
Shibutani, S., Dasaradhi, L., Terashima, I., Banoglu, E., and Duffel, M.W. 1998. Alpha-Hydroxytamoxifen is a substrate of hydroxysteroid (alcohol) sulfotransferase, resulting in tamoxifen DNA adducts. Cancer Research, 58:647-654.
Duffel, M.W., Chen, G., and Sharma, V. 1998. Studies on an affinity label for the sulfuryl acceptor binding site in an aryl sulfotransferase. Chemico-Biological Interactions, 109:81-92.
Shibutani, S., Shaw, P.M., Dasaradhi, L., Duffel, M.W., and Terashima, I. 1998. Sulfation of a-hydroxytamoxifen catalyzed by human hydroxysteroid sulfotransferase results in tamoxifen-DNA adducts. Carcinogenesis, 19:2007-2011.
Banoglu, E. and Duffel, M.W. 1997. Studies on the interactions of chiral secondary alcohols with rat hydroxysteroid sulfotransferase STa. Drug Metabolism and Disposition, 25:1304-1310.

 

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