School of Health Sciences - Research in Toxicology

Dr. Gary Carlson is examining the relationship between the metabolism of chemicals and their toxic actions. This includes an interest in both activation and detoxification pathways in the liver and other target organs. Current studies utilize a variety of techniques ranging from isolated cells to whole animals to examine the biochemical mechanisms by which chemical agents exert their toxic and carcinogenic actions. Particular attention focuses on the lung as both a target tissue and a major organ of bioactivation of chemicals that produce either pneumotoxicity and/or systemic toxicity. Emphasis is placed on substrates of the pulmonary cytochrome P450 2F, which is involved in the activation of a number of toxic and carcinogenic small molecular weight compounds. Of particular interest is styrene which is both pneumotoxic and causes lung tumors in mice. Studies are focusing on possible modes of action including oxidative stress and the possible involvement of the Clara cell protein CC10. Additional chemicals of interest include benzene, carbon tetrachloride and ethyl carbamate (urethane).

Dr. Wei Zheng's research focuses on understanding of the role of brain barrier systems in metal-induced neurotoxicities, the environmental causes of neurodegenerative diseases and essential tremors, and the therapeutic approach in treatment of metal-induced toxicities. More specifically, his group investigates the molecular mechanism by which metal transporters in brain barriers exert diverse responses to exposures to manganese (Mn) or iron (Fe), two metals known to play roles in parkinsonian movement disorders. Dr. Zheng also translates the laboratory discoveries to human populations by using molecular techniques to screen Fe metabolism proteins in body fluids of welders and smelters, aiming at discovery of biomarkers for early diagnosis of manganism. Recently, his laboratory discovers that the blood-CSF barrier possesses a remarkable capacity in sequestering and metabolizing beta-amyloid, a culprit in the etiology of Alzheimer's disease. Current work by his students and post/doc fellows is directed toward a better understanding of how brain cleanses beta-amyloids and how the aging and toxic exposure may alter this process. Additionally, Dr. Zheng's group is developing a better regimen for applying an antituberculosis drug para-aminosalicylic acid (PAS) in treatment of Mn-induced Parkinsonism.