BS - Carrol College, Waukesha, WI - 1978
MS - Microbiology/Biology, University of Wisconsin, Oshkosh - 1985
PhD - Biological Sciences, University of Wisconsin, Milwaukee - 1987
Reductive metal metabolism
The exposure to certain metals in the environment, water and food supplies, and the workplace can pose a major health hazard. Prime examples include lead poisoning, chromium-related carcinogenesis, and neurologic effects associated with increased intake of metals such as manganese. Our understanding of the metabolism of these metals and their cycling in the environment is limited. It is known, however, that reductive reactions play a role in both the potential toxic effects of these metals and in the mobilization of these metals in the environment. Recent studies in both animals and microbes have indicated a strong role for certain electron-carrier proteins in reductive metal metabolism. Research in my laboratory involves the elucidation of the role of cytochromes and other electron-transporting proteins in reductive metal metabolism.
Reductive Chromium Metabolism
Exposure to chromium (Cr) compounds is associated with serious damage to internal organs and increased incidence of respiratory tract cancer. The reductive metabolism of Cr(VI) to Cr(III), via reactive intermediates, is thought to play a key role in the cytotoxicity, mutagenicity, and carcinogenicity of Cr. The mechanisms of Cr(VI) reduction in humans are distinct from those reported in rodent models. We are therefore investigating the role of human microsomal enzymes (P450 reductase, cytochrome b5, b5 reductase) in the reduction of Cr(VI) in order to better understand their potential role in mediating cell damage associated with CR(VI) exposure (e.g. free radical attack, lipid peroxidation, DNA strand breaks, etc.).
Reductive Iron and Manganese Metabolism
Recent studies with a microbial model indicate a strong role for electron-transport proteins in the reductive metabolism of metals such as manganese (Mn) and iron (Fe). Our goals are to examine, in detail, the enzymes responsible for metal reduction in this model system. This will greatly enhance our understanding of how cells interact with metals and of how these processes affect the availability of metals to biological systems. Both biochemical and molecular approaches are being used to elucidate the identity, role, and membrane topology of components required for metal reduction, including quinones, cytochromes, and flavoproteins.