UW-Madison School of Pharmacy

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Lauren Trepanier, D.V.M., PhD

Affiliate Professor, School of Pharmacy
Professor, Dept of Medical Sciences, School of Veterinary Med

 

 

 


Our laboratory is interested in the role of drug reduction pathways in the toxicity of arylamine compounds, including both therapeutic drugs and environmental carcinogens. Arylamines become toxic through the formation of hydroxylamine metabolites. We have characterized the enzymatic detoxification of hydroxylamines by a novel xenobiotic reduction pathway, comprised of cytochrome b5 and NADH cytochrome b5 reductase. We are working to identify pharmacogenetic variability in this pathway, and its relationship to drug hypersensitivity to the arylamine antimicrobial sulfamethoxazole. We are also examining the role of variability in the expression of cytochrome b5 and NADH cytochrome b5 reductase, and the development of DNA adducts in tissues exposed to the arylamine carcinogens.

Background: Lauren received her DVM from Cornell University (1986) and a PhD in Pharmacology from Cornell University (1997). She is board certified in Internal Medicine and Clinical Pharmacology. She joined the faculty of the School of Veterinary Medicine in 1997, and joined Pharmaceutical Sciences as an Affiliate Assistant Professor in 2001.

Professional Interests: Metabolic basis of idiosyncratic drug toxicity; pharmacogenetics.

Highlighted Publications:
  • Kurian JR, Longlais BJ, Trepanier LA. Discovery and characterization of a cytochrome b5 variant in humans with impaired hydroxylamine reduction capacity. Pharmacogenetics and Genomics (in press).
  • Kurian JR, Chin NA, Longlais BJ, Hayes KL, Trepanier LA. Reductive detoxification of arylhydroxylamine carcinogens by human NADH cytochrome b5 reductase and cytochrome b5. Chem Res Toxicol 19: 1366-73, 2006.
  • Lavergne SN, Danhof R, Volkman E, Trepanier LA. Association of drug-protein adducts and anti-drug antibodies in a clinical model of sulfonamide hypersensitivity. Clin Exp Allergy 36: 907-15, 2006.
  • Lavergne SN, Kurian JR, Bajad SU, Maki JE, Yoder AE, Guzinski MV, Graziano FM, Trepanier LA. Roles of endogenous ascorbate and glutathione in the cellular reduction and cytotoxicity of sulfamethoxazole-nitroso. Toxicology 222: 25-36, 2006.
  • Trepanier LA, Bajad SU, Kurian JR. Evaluation of the cytochrome b5 / cytochrome b5 reductase pathway Current Protocols in Toxicology (invited review) 4.16.1-4.16.17, 2005.
  • Lavergne SN, Volkmann EM, Maki JE, Yoder AR, Trepanier LA. Evaluation of the clinical, immunologic, and biochemical effects of sulfamethoxazole-nitroso administration to dogs: a pilot study. Toxicology 208: 63-72, 2005.
  • Trepanier LA, Yoder AR, Bajad S, Beckwith MD, Bellehumeur JL, Graziano FM. Plasma ascorbate deficiency is associated with impaired reduction of sulfamethoxazole nitroso in HIV infection. J Acquir Immunodef Syndr 36: 1041-1050, 2004.
  • Trepanier LA. Idiosyncratic toxicity associated with potentiated sulfonamides in the dog. J Vet Pharmacol Ther 27: 129-138, 2004.
  • Kurian JR, Bajad S, Miller JL, Chin N, Trepanier LA. NADH cytochrome b5 reductase and cytochrome b5 catalyze the microsomal reduction of xenobiotic hydroxylamines and amidoximes in humans. J Pharmacol Exp Ther 311:1171-8, 2004.
  • Trepanier LA, Danhof R, Toll J, Watrous D. Clinical findings in 40 dogs with hypersensitivity associated with potentiated sulfonamides. J Vet Intern Med 17: 647-652, 2003.