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Lucy Waskell, MD, PhD
Director of Anesthesiology Research, Veterans' Administration
Professor of Anesthesiology
Phone: 734-845-5858
Fax: 734-845-3096
Email: waskell@umich.edu
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Research Interests:
For over 25 years, the National Institutes of Health and the Veterans Administration have supported Dr. Waskell's research on the drug metabolizing enzyme, cytochrome P450. Humans possess 57 different cytochromes P450, which in addition to determining the duration of action, toxicity, and in many instances the activity of most of the drugs in clinical use, also mediate the biosynthesis and degradation of a cornucopia of endogenous compounds such as glococorticoids, sex steroids, bile acids, prostaglandins, and vitamins A and D. Dr. Waskell's laboratory is investigating how cytochrome P450 and its helper proteins, cytochrome b5 and cytochrome P450 reductase, are able to metabolize such a great variety of compouds. Currently protein engineering, X-ray crystallography, and biochemical techniques are being employed to assist in unraveling the mechanistic secrets of these essential enzymes.
Recent Publications:
Sheng X, Zhang H, Im SC, Horner JH, Waskell L, Hollenberg PH, Newcomb M. Kinetics of oxidation of benzphetamine by compounds I of cytochrome P450 2B4 and its mutants. J Am Chem Soc. 2009 Feb 11. [PubMed]
Hamdane D, Xia C, Im SC, Zhang H, Kim JJ, Waskell L. Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450. J Biol Chem. 2009 Apr 24; 284(17):11374-84. [PubMed]
Xu J, Durr UH, Im SC, Gan Z, Waskell L, Ramamoorthy A. Bicelle-enabled structural studies on a membrane-associated cytochrome B5 by solid-state MAS NMR spectroscopy. Angew Chem Int Ed Engl. 2008; 47(41):7864-7. [PubMed]
Mak PJ, Im SC , Zhang H., Waskell L, Kincaid JR. Resonance Raman studies of cytochrome P450 2B4 in its interactions with substrates and redox partners. Biochemistry 47(12): 3950-3963, Mar 25, 2008. [PubMed]
Zhang H, Hamdane D, Im SC , Waskell L. Cytochrome b5 inhibits electron transfer from NADPH-cytochrome P450 reductase to ferric cytochrome P450 2B4. J Biol Chem, 283(9): 5217-5225. Feb, 29, 2008. [PubMed]
Lin HL, Myshkin E, Waskell L. Peroxynitrite activation of human cytochrome P450s 2B6 and 2E1: heme modification and site-specific nitrotyrosine formation. Chem Res Toxicol 20(11):1612-22, Nov. 2007 [PubMed]
Zhang H, Im S-C, Waskell L. Cytochrome b5 increases the rate of product formation by cytochrome P450 2B4 and competes with cytochrome P450 reductase for a binding site on cytochrome P450 2B4. J Biol Chem 282(41): 29766-76, Oct. 12, 2007 [PubMed]
Durr UHN, Waskell L, Ramamoorthy A. The cytochromes P450 and b5 and their reductases-Promising targets for structural studies by advanced solid-state NMR spectroscopy. Biochim Biophys Acta. 1768(12):3235-59. Aug. 24 2007 [PubMed]
Durr UHN, Yamamoto K, Im SC, Waskell L, Ramamoorthy A. Solid-state NMR reveals structural and dynamical properties of a membrane-anchored electron-carrier protein, cytochrome b(5). Journal of the American Chemical Society, 129 (21): 6670-1 May 30 2007. [PubMed]
Kobayashi Y, Sridar C, Kent UM, Puppali SG, Rimoldi JM, Zhang H, Waskell L, Hollenberg PF. Structure-Activity Relationship and Elucidation of the Determinant Factor(s) Responsible for the Mechanism-Based Inactivation of P450 2B6 by Substituted Phenyl Diaziridines. Drug Metab Dispos. 34:2102-10, 2006. [PubMed]
Z hang H, Myshkin E, Waskell L. Role of cytochrome b5 in catalysis by cytochrome P450 2B4. Biochemical and Biophysical Research Communications 338: 449-506, 2005. [PubMed]
Lin HL, Zhang H, Waskell L, Hollenberg PF. The highly conserved Glu149 and Tyr190 residues contribute to peroxynitrite-mediated nitrotyrosine formation and the catalytic activity of cytochrome P450 2B1. Chem Res Toxicol 18: 1203-10, 2005. [PubMed]
Deep S, Im SC, Zuiderweg ER, Waskell L. Characterization and calculation of a cytochrome c-cytochrome b(5) complex using NMR data. Biochemistry 44: 10654-68, 2005. [PubMed]
Cournoyer JJ, Pitman JL, Ivleva VB, Fallows E, Waskell L, Costello CE, O'Connor PB. Deamidation: Differentiation of aspartyl from isoaspartyl products in peptides by electron capture dissociation. Protein Science 14:452-463, 2005. [PubMed]
Research Divisions |
