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Toxicology

Graduate Faculty Research Interests

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Drugs, dietary compounds and environmental contaminants are often lipid soluble and therefore penetrate cell membranes readily. As a result these substances are extensively absorbed and widely distributed among organ and cell systems. These foreign chemicals may interact with macromolecular targets on the surface of cell membranes as well as within cells, sometimes leading to toxic manifestations, but other times protecting normal cellular functions. Fortunately, the body contains a variety of "defense" mechanisms to chemical exposure; these include a range of transporter proteins that facilitate or prevent uptake, a wide variety of enzymes that act to enhance the water solubility of foreign chemicals to promote their elimination from the body, and enzymatic systems that can repair injured cells.

These defenses, however, represent a "double-edged sword"; that is, they may decrease the effectiveness of life-saving drugs and/or decrease the net absorption of beneficial dietary components, such as antioxidants. In addition, enzymatic transformation of foreign compounds may lead to the formation of toxic metabolites that can attack protein, lipid and nucleic acid targets within cells. These reactions are now known to underlie the cytotoxic and carcinogenic actions of many environmental chemicals. Furthermore, some of these metabolites may selectively induce oxidative stress within specific cell types, potentially contributing to vascular and neurodegeneratvie diseases and premature aging.

The focus of the studies in this track is to explore the fundamental mechanisms underlying cellular defenses and how their normal operation or failure can lead to beneficial or adverse effects of drugs and other foreign chemicals. Numerous research opportunities related to drug transport and metabolism, and chemical-induced cell injury, death and regeneration are available. The faculty in this track offer a set of courses in basic and advanced principles of drug metabolism/transport and toxicology.

In addition, enzymatic transformation of foreign compounds may lead to the formation of toxic metabolites that can attack protein, lipid and nucleic acid targets within cells. These reactions are now known to underlie the cytotoxic and carcinogenic actions of many environmental chemicals. Furthermore, some of these metabolites may selectively induce oxidative stress within specific cell types, potentially contributing to vascular and neurodegeneratvie diseases and premature aging. The focus of the studies in this track is to explore the fundamental mechanisms underlying cellular defenses and how their normal operation or failure can lead to beneficial or adverse effects of drugs and other foreign chemicals. Numerous research opportunities related to drug transport and metabolism, and chemical-induced cell injury, death and regeneration are available. The faculty in this track offer a set of courses in basic and advanced principles of drug metabolism/transport and toxicology.