UR Faculty: M. W. Anders, D.V.M., Ph.D.

D.V.M. (1960)
Iowa State University
Ph.D. (1964)
University of Minnesota, Minneapolis

M. W. Anders, D.V.M., Ph.D.
Professor Emeritus of Pharmacology and Physiology, of Anesthesiology, and of Environmental Medicine

Primary Appointment:
Pharmacology and Physiology

GEBS Cluster Affiliations:
CMM-Cellular and Molecular Basis of Medicine
TOX-Toxicology

Research:
Bioactivation and biotransformation of xenobiotics

Anders's Lab Page

Contact Information:
E-mail: MW_Anders@urmc.rochester.edu

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, New York 14642

Medical Center, Room 4-8553
Phone: (585) 275-1678
Fax: (585) 273-2652

Research Overview

The objective of our research is to understand the mechanisms by which drugs and chemicals produce cell and organ toxicity and the role of cellular cytoprotective mechanisms in modulating toxicity. The toxicity of most organic chemicals is associated with their biotransformation to reactive, electrophilic metabolites or to stable, but toxic, metabolites that cause cell damage. We are particularly interested in three aspects of chemical bioactivation: one, what is the chemical nature of the metabolites formed; two, what enzymes are involved in the formation of toxic metabolites; and, three, how is the formation of toxic metabolites coupled to the production of cell damage? Several approaches are used to investigate the bioactivation of chemicals. Reaction mechanism studies are conducted to understand the metabolic pathways involved and to gain insight into the nature of reactive intermediates, which may be too short-lived to be isolated. Studies on the perturbation of cellular glutathione homeostasis are employed to examine the relationships between toxic metabolite formation and cell damage. Several techniques are used, including mass spectrometry and nuclear magnetic resonance spectroscopy, to identify metabolites, immunohistochemistry to map the distribution of bioactivation and cytoprotective pathways, and development of transfected cell lines to study drug-induced cell damage. Present studies are focused on the glutathione-dependent bioactivation of halogenated alkenes and haloacids, on the enzymology and regulation of glutathione biosynthesis, and on the enzymology of the mercapturic acid pathway, including cytosolic and microsomal glutathione transferases, cysteine S-conjugate N-acetyltransferase, and acylase. New studies on the selective targeting of cytoprotective chemicals to cellular organelles, i.e., mitochondria, have just begun.

Recent Publications

Anders MW. (2005) Formation and toxicity of anesthetic degradation products. Annu. Rev. Pharmacol. Toxicol. 45:147-176.

Board PG and Anders MW (2005) Human glutathione transferase zeta. Methods Enzymol. 401:61-77.

Anders MW, Robotham JL, and Sheu SS (2006) Mitochondria: new drug targets for oxidative stress-induced diseases. Expert Opin. Drug Metab. Toxicol. 2:71-79.

Blackburn AC, Matthaei KI, Lim C, Taylor MC, Cappello JY, Hayes JD, Anders MW, and Board PG (2006) Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways. Mol. Pharmacol. 69:650-657.

Fang YY, Kashkarov U, Anders MW, and Board PG (2006) Polymorphisms in the human glutathione transferase zeta promoter. Pharmacogenet. Genomics 16:307-313.

Sheu SS, Nauduri D, and Anders MW (2006) Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim. Biophys. Acta 1762:256-265.

Starr TB, Matanoski G, Anders MW, and Andersen ME (2006) Workshop overview: reassessment of the cancer risk of dichloromethane in humans. Toxicol. Sci. 91:20-28.

Xu L, Krenitsky DM, Seacat, AM, Butenhoff JL, Tephly .TR, and Anders MW (2006) N-Glucuronidation of perfluorooctanesulfonamide by human, rat, dog, and monkey liver microsomes and by expressed rat and human UDP-glucuronosyltransferases. Drug Metab.Dispos., in press.

PubMed Publication List

PubMed is maintained by the National Library of Medicine and provides complete abstracts of all 'anders mw' publications, as well as links to the full text of many articles (at journal homepages).

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GEBS Clusters:

CMM

TOX