Division of Medicinal and Natural Products Chemistry
Department of Pharmaceutical Sciences and Experimental Therapeutics
College of Pharmacy, The University of Iowa
115 S. Grand Ave., S325 PHAR
Iowa City, IA 52242-1112
BS, Chemistry, University of Texas at Austin, 1975
PhD, Chemistry (Biochemistry), University of Texas at Austin, 1979
1979-1981, National Institutes of Health, Enzyme and Cellular Biochemistry Section, Laboratory of Biochemistry and Metabolism, NIDDK, Staff Fellow
1981-1986, University of Iowa, College of Pharmacy, Assistant Professor
1986-1993, University of Iowa, College of Pharmacy, Associate Professor
1993-present, University of Iowa, College of Pharmacy, Professor
1995-present, University of Iowa, College of Pharmacy, Professor and Associate Dean for Research and Graduate Programs
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. One major current research project includes investigations on the mechanism and catalytic regulation of aryl and alcohol sulfotransferases along with development of methods to discover highly selective inhibitors of individual sulfotransferases. Another major research effort is directed towards understanding how polychlorinated biphenyls and their hydroxylated metabolites alter the regulation and catalytic function of the hydroxysteroid sulfotransferases.
Ekuase, E.J., Lehmler, H.J., Robertson, L.W., Duffel, M.W. 2014. Binding interactions of hydroxylated polychlorinated biphenyls (OHPCBs) with human hydroxysteroid sulfotransferase hSULT2A1. Chem Biol Interact., 212:56-64.
Qin, X., Lehmler, H.J., Teesch, L.M., Robertson, L.W., Duffel, M.W. 2013. Chlorinated biphenyl quinones and phenyl-2,5-benzoquinone differentially modify the catalytic activity of human hydroxysteroid sulfotransferase hSULT2A1. Chem Res Toxicol. 26(10):1474-85.
Lehmler, H.J., He, X., Li, X., Duffel, M.W., Parkin, S. 2013. Effective synthesis of sulfate metabolites of chlorinated phenols. Chemosphere. 93(9):1965-71.
Grimm, F.A., Lehmler, H.-J., He, X., Robertson, L.W., and Duffel, M.W. 2013. Sulfated Metabolites of Polychlorinated Biphenyls are High-Affinity Ligands for the Thyroid Hormone Transport Protein Transthyretin. Environmental Health Perspectives, 121:657-662.
Qin, X., Teesch, L.M. and Duffel, M.W. 2013. Modification of the Catalytic Function of Human Hydroxysteroid Sulfotransferase hSULT2A1 by Formation of Disulfide Bonds. Drug Metabolism and Disposition, 41:1094-1103.
Wu, X., Kania-Korwel, I., Chen, H., Stamou, M., Dammanahalli, K.J., Duffel, M.W., Lein P.J., and Lehmler, H.-J. 2013. Metabolism of 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) Atropisomers in Tissue Slices from Phenobarbital or Dexamethasone-Induced Rats is Sex-Dependent. Xenobiotica, 43(11):933-47.
Lehmler, H.-J., He, X., Duffel, M.W., and Parkin, S. 2013. “3,4’5-Trichlorobiphenyl-4-yl 2,2,2-trichloroethyl sulfate.” Acta Cryst., E69 (Pt 4):o620.
Dhakal, K., He, X., Lehmler, H.-J., Teesch, L.M., Duffel, M.W. and Robertson, L.W. 2012. “Identification of sulfated metabolites of 4-chlorobiphenyl (PCB3) in the serum and urine of male rats.” Chemical Research in Toxicology, 25:2796-2804.
Dammanahalli, J.K. and Duffel, M.W. 2012. Oxidative modification of rat sulfotransferase 1A1 activity in hepatic tissue slices correlates with effects on the purified enzyme. Drug Metabolism and Disposition, 40:298-303.
Gulcan, H.O. and Duffel, M.W. 2011. Substrate Inhibition in human hydroxysteroid sulfotransferase SULT2A1: studies on the formation of catalytically non-productive enzyme complexes. Archives of Biochemistry and Biophysics, 507:232-240.
Liu, Y., Lehmler, H.-J., Robertson, L.W., and Duffel, M.W. 2011. Physicochemical properties of hydroxylated polychlorinated biphenyls aid in predicting their interactions with rat sulfotransferase 1A1 (rSULT1A1). Chemico-Biological Interactions, 189:153-160.
Ekuase, E., Liu, Y., Lehmler, H.-J., Robertson, L.W., and Duffel, M.W. 2011. Structure-activity relationships for hydroxylated polychlorinated biphenyls as inhibitors of the sulfation of dehydroepiandrosterone catalyzed by human hydroxysteroid sulfotransferase SULT2A1. Chemical Research in Toxicology, 24:1720-1728.
Joshi, S. N., Vyas, S. M., Duffel, M. W., Parkin, S., and Lehmler, H.-J. 2011. Synthesis of sterically hindered polychlorinated biphenyl derivatives. Synthesis, 7:1045-1054.
Joshi, S.N., Vyas, S.M., Wu, H., Duffel, M.W., Parkin, S., and Lehmler, H-J. 2011 Regioselective iodination of aromatic compounds using silver salts. Tetrahedron, 67:7461-7469.
Kania-Korwel, I., Duffel, M.W., and Lehmler, H-J. 2011. Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes. Environmental Science and Technology, 45:9590-9596.
Wu, X. Pramanik, A., Duffel, M.W., Hrycay, E.G., Bandiera, S.M., Lehmler, H.-J., and Kania-Korwel, I. 2011. 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) is enantioselectively metabolized to hydroxylated metabolites by rat liver microsomes. Chemical Research in Toxicology, 24:2249-2257.
Duffel, M.W. 2010. Sulfotransferases. In, Biotransformation: Volume 4 of Comprehensive Toxicology (F.P. Guengerich, ed.). Elsevier, Oxford, 367-384.
Li, X., Parkin, S., Duffel, M.W., Robertson, L.W., Lehmler, H.-J. 2010. An efficient approach to sulfate metabolites of polychlorinated biphenyls. Environment International. 36:843-8.
Liu, Y., Smart, J., Song, Y., Lehmler, H.-J., Robertson, L.W., and Duffel, M.W. 2009. Structure-activity relationships for hydroxylated polychlorinated biphenyls as substrates and inhibitors of rat sulfotransferases and modification of these relationships by changes in thiol status. Drug Metabolism and Disposition, 37:1065-1072.
Wangpradit, O., Mariappan, S., Teesch, L., Norstrom, K., Duffel, M.W., Robertson, L., and Luthe, G. 2009. Novel biotransformation by prostaglandin H synthase generates highly toxic electrophilic metabolites. Chemical Research in Toxicology, 22:64-71.
Gulcan, H.O., Liu, Y., and Duffel, M.W. 2008. Pentachlorophenol and other chlorinated phenols are substrates for human hydroxysteroid sulfotransferase hSULT2A1. Chemical Research in Toxicology, 21:1503-1508.
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 Disposistion, 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.
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.