William M. Valentine, Ph.D., D.V.M.

Associate Professor of Pathology

Ph.D., University of Illinois, Chicago, 1983 (Physiology and Biophysics)

D.V.M., University of Illinois, Champaign, 1985 (Veterinary Medicine)

This laboratory is investigating the mechanisms of environmental neurotoxicants and the cellular processes responsible for axonal degeneration. Current experiments focus on the role of copper accumulation and oxidative stress in dithiocarbamate-mediated segmental demyelination, using proteomic methods to delineate protein modifications occurring during axonal degeneration. For dithiocarbamates structure-activity relationships that contribute to neurotoxicity are currently being characterized, and the requirement of lipid peroxidation and copper accumulation for neurotoxicity is being determined. Related experiments are defining the sites of protein oxidative damage, characterizing the cellular responses to injury, and using transgenic models with compromised defense to oxidative injury to assess the potential for individual susceptibilitites to this commonly used class of compounds. These studies will help to 1) identify agents that may act through similar mechanisms before human exposures occur, 2) identify susceptible populations, and 3) predict the affects of long term low level exposures to these commonly used agents. Axonal degeneration is the most prevalent type of peripheral neuropathy in humans and can result from injury, toxicity, and metabolic, heritable, immune-mediated, or ischemic disorders. The potential of proteomic analysis for delineating the post-translational modifications of proteins responsible for initiating and executing axonal degeneration is being explored. The sequence of changes in the proteome of peripheral nerve undergoing axonal degeneration as a function of time subsequent to injury is being correlated with structural changes assessed by light and electron microscopy with the goals of 1) improving the ability to detect and diminish the extent of axonal degeneration and 2) identifying targets for promoting regeneration within the nervous system.

Recent Publications

Valentine H, Amarnath K, Amarnath V, Li W, Ding X, Valentine WM, Ichihara G. Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure. Toxicol Sci. 2007 98:427-35.

Valentine HL, Does MD, Marshall V, Tonkin EG, Valentine WM. Multicomponent T(2) analysis of dithiocarbamate-mediated peripheral nerve demyelination. Neurotoxicology. 2007 28:645-54.

Valentine HL, Amarnath K, Amarnath V, Valentine WM. Dietary copper enhances the peripheral myelinopathy produced by oral pyrrolidine dithiocarbamate. Toxicol Sci. 2006 89:485-94.

Valentine WM, Hill KE, Austin LM, Valentine HL, Goldowitz D, Burk RF. Brainstem axonal degeneration in mice with deletion of selenoprotein p. Toxicol Pathol. 2005 33:570-6.

Sills RC, Harry GJ, Valentine WM, Morgan DL. Interdisciplinary neurotoxicity inhalation studies: Carbon disulfide and carbonyl sulfide research in F344 rats. Toxicol Appl Pharmacol. 2005 207:245-50.