Michael Franklin

 

Michael Franklin

Title:

Professor


Email:

Michael.Franklin@pharm.utah.edu



Education:

 

B.S., 1966, University of Birmingham

Ph.D., 1969, University of London, Biochemistry




 

Research Interests

 

Dr. Franklin is now enjoying his retirement status, but maintains an office and a presence in the Department and College, and is available for consultation.  Before retirement his research group centered its investigations around the enzymes responsible for the disposition of xenobiotic compounds. Xenobiotics include drugs, environmental contaminants and natural products. Many xenobiotics are capable of causing toxicity by interacting with cellular targets, either directly, or most often, after bioactivation by certain of the metabolizing enzymes. This can be prevented through further metabolism by an inactivating or protective set of metabolizing enzymes or by active excretion before the toxic interaction can occur. The laboratory was especially interested in factors which perturb the balance of activation/inactivation enzymes The enzymes studied included cytochromes P450, epoxide hydrolase, quinone oxidoreductase, and UDPglucuronosyltransferases, sulfotransferases and glutathione transferases. Of greatest interest were changes in activities from alterations in transcription rate, and direct inhibition, and how such changes arise from the influence of hormones, administered drugs, and environmental and other chemicals. The expertise of the research group was utilized in studies over a wide range of diseases and pharmacological agents, and most recently, how natural products present in traditional medicines in Papua New Guinea might interfere with the anti-retroviral therapy in people living with AIDs. In conjunction with investigators in the Division of Hematology, how variations in certain of these metabolizing enzymes contribute to the precipitation of Porphyria Cutanea Tarda was under scrutiny. In the recent past, and in conjunction with information generated by neuroscientists, studies on how candidate antiseizure and antiepileptic medications affect metabolizing enzymes was an important component in their potential as therapeutic agents. How drug metabolizing and other enzymes were perturbed by selenazolidines, novel prodrug forms of L-selenocysteine that were designed and synthesized locally, was an important consideration in their evaluation as chemopreventive and cytoprotective compounds.




 

Selected Publications

 

Haley, S.L., Lamb, J.G., Franklin, M.R., Constance, J.E., Dearing, D.M. (2007) Xenobiotic metabolism of plant secondary compounds in juniper (Juniperus monosperma) by specialist and generalist woodrat herbivores, genus Neotoma. Comp Biochem Physiol C Toxicol Pharmacol. 146, 552-560

White, H.S., Franklin, M.R., Kupferberg, H.J., Schmutz, M., Stables, J.P., and Wolf H.H. (2008) The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models.  Epilepsia 49, 1213-1220

Franklin, M.R., and Hathaway L.B. (2008) 2-Diethylaminoethyl-2,2-diphenylvalerate-HCl (SKF525A) Revisited: Comparative Cytochrome P450 Inhibition in Human Liver Microsomes by SKF525A, its Metabolites, and SKF-Acid and SKF-Alcohol.  Drug Metab Dispos. 36, 2539-2546.

Arch, D.D., Bergonia, H.A., Hathaway, L., Kushner, J.P,, Phillips, J.D., and Franklin, M.R., (2009) Longitudinal Study of a Mouse Model of Familial Porphyria Cutanea Tarda.  Cell. Molec. Biol. 55, 46-54.

Barker, M.L., Hathaway, L.B., Arch, D.D., Westbroek, M.L., Kushner,J.P., John D. Phillips, J.D., and Franklin, M.R. (2009) Hyper- and Hypo- Induction of Cytochrome P450 activities with Aroclor 1254 and 3-Methylcholanthrene in Cyp1a2(-/-) mice.  Chem.-Biol Interactions 182, 220-226

El-Sayed, W.M., Tarek Aboul-Fadl, T., and Franklin, M.R., (2010) Effects of Isatin-isoniazid Derivatives on Drug Metabolizing and Chemoprotective Enzymes in Mice.  Drug Development Res. 71, 313-32

Lamb, J.G., Hathaway, L.B., Munger, M.A., Raucy, J.L., Franklin, M.R., (2010) Nano-silver Particle Effects on Drug Metabolism in Vitro.  Drug Metab Dispos. 38,  2246-2251.

Phillips, J.D., Kushner, J.P., Bergonia, H.A., and Franklin, M.R. (2011) Uropophyria in the Cyp1a2-/- mouse. Blood Cells Mol. Dis. 47 249-254.

Ali A, Dua Y, Constance J.E., Franklin M.R., and Dudek F.E. (2012) A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models. Epilepsia  53  196-206.

Poerschke, R.L., Franklin M.R., Bild, A.H. and Moos, P.J. (2012) Major differences among chemopreventive organo-selenocompounds in the sustained elevation of cytoprotective genes. J Biochem Mol Toxicol. 26  344-353

Kuzbari, O., Peterson C.M., Franklin M.R., Hathaway, L.B., Johnstone, E.B., Hammoud, A.O., and Lamb, J.G. (2013) Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms. Reprod Toxicol. 37 24-30

Larson, E.C., Hathaway, L.B., Lamb J.G., Pond C.D., Rai, P.P., Matainaho T.K., Piskaut, P., Barrows, L.R. and Franklin M.R. (2014) Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy.  J. Ethnopharmacology  155 1433-1440

 

 

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