Education and Training
B.S. 1985, University California, Irvine
M.A. 1988, California State University, Fullerton
Ph.D. 1994, University of California, San Diego
Post-doctoral fellow 1994-1996, Karolinska Institute, Stockholm, Sweden
Research Interests
Organisms come into contact with numerous endogenous and exogenous xenobiotic compounds that must be removed by drug metabolizing/elmination enzymes. Reactions involved in drug metabolism are often classified as phase I (activation) and phase II (detoxification) and phase III (elimination) reactions. Enzymes catalyzing phase I reactions include cytochrome P450 enzymes. Enzymes catalyzing phase II reactions include the conjugation enzymes UDP-glucuronosyltransferases (UGT), glutathione S-transferases (GST) as well as other enzymes that protect the cell from toxic damage due to oxidative stress, NAD(P)H quinone oxidoreductase (QOR) and microsomal epoxide hydroxylase (mEH). Phase III enzymes include ATP-binding cassette (ABC) transporters. Phase I, phase II, and phase III enzymes acting in concert, remove xenobiotic compounds via the bile or urine.
Phase I, phase II, and phase III enzymes are subject to induction by a variety of chemical agents. The regulation of the expression of these enzymes is important because they effect the clearance of numerous drugs and other exogenous and endogenous substances from the body.
Research in the laboratory is focused on the study of the molecular mechanisms that govern the regulation of the induction of drug metabolizing/elimination enzymes in the liver and brain tissue. Research is performed in collaboration with the Anticonvulsant Drug Development (ADD) Program (www.pharmacy.utah.edu/pharmtox/ADD/main.html) in the screening of potential antiepileptic agents to induce drug metabolizing/elimination enzymes. Studies are underway to examine the molecular mechanisms underlining therapy resistant epilepsy.
Research is also performed in collaboration with Dr. Denise Dearing in the department of Biology to study the ability of mammalian herbivore species to detoxify plant chemical toxins.
Laboratory methods utilized to carry out our research include in vivo drug screening studies, as well as in vitro cell culture systems, subcellular organelle isolation by differential centrifugation, biochemical enzyme assay, TLC and HPLC analysis. Molecular techniques include cDNA cloning, Northern blot analysis, as well as real-time PCR analysis of mRNA, EMSA analysis of nuclear transcription factors and Luciferase reporter systems.
Selected Publications
Lamb, J.G., and Tukey, R.H. Cloning and characterization of cDNAs encoding mouse Ugt1.6 and rabbit UGT1.6: Differential induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochemistry, 1994, 33: 10513-10520.
Hellmold, H., Lamb, J.G., Wyss, A., Gustafsson, J-Å., and Warner, M. Developmental and endocrine regulation of P450 isoforms in rat breast. Molecular Pharmacology, 1995, 48: 630-638.
Lamb, J.G. and Franklin, M.R. (2000) Early events in the induction of rat hepatic drug metabolizing enzymes by 1,7-phenanthroline: Direct comparison with oltipraz and tert-butyl-4-hydroxyanisole. Drug Metabolism and Disposition, 2000, 28, 1018-1023.
Lamb, J.G., and Franklin, M.R. (2002) Cell-based studies reveal differences in glutathione S-transferase induction between oltipraz and tert-butylhydroquinone. J. Biochem. Mol. Tox., Drug Metabolism and Disposition, 2000, 28, 1018-1023.
Lamb, J.G., Franklin, M.R., Smith-Yockman, M.D., Wilcox, K.S., and White, H.S. Induction of multidrug transporter and drug metabolism mRNAs in rat liver by kainic acid induced seizures: Implications for therapy resistant epilepsy. 2004, Epilepsia 45 (s7),p 12.
Lamb, J.G., Smith-Yockman, M.D., Constance, J., Poerschke, R., Franklin, M.R., and White, H.S. Effect of polychlorinated biphenyl (PCB) on the anticonvulsant efficacy of phenytoin in rats. 2006, Epilepsia, 47 (s4) p. 223.
Haley SL, Lamb JG, Franklin MR, Constance JE, Denise Dearing M. Xenobiotic metabolism of plant secondary compounds in juniper (Juniperus monosperma) by specialist and generalist woodrat herbivores, genus Neotoma. 2007 Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology 146(4) p. 552-560.
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