Humans are exposed, both intentionally and accidentally, to a wide variety of foreign compounds, known as "xenobiotics,” via the processes of absorption, ingestion and inhalation. Many xenobiotics are potentially harmful to the body, and cause toxicity after chemical transformation by drug metabolism enzymes in specific cells, often in specific organs of the body. It is easy to envision how drugs affect the body, but it is also important to recognize that the body affects the fate of drugs that are administered. The processes of absorption, distribution, metabolism, and elimination are vitally important to drug action and toxicities. Research on the enzymes and the enzyme substrates that are drugs is the general area of drug metabolism, and research in this field within the Department is closely aligned with biochemical toxicology research. Of particular interest to department faculty are the cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, and the xenobiotic transporter proteins that are important in metabolizing or transporting many drugs used to treat disease, in addition to xenobiotic toxicants.
Biochemical toxicologists in the Department investigate enzyme mechanisms, regulation of drug metabolism genes, genetic factors that cause individual differences in responsiveness to xenobiotics, features that cause drug/drug interactions, and bioactivation of xenobiotics to toxic intermediates. Much of this research is focused on enzymes, transporters, and cellular processes in specific organs, such as liver, lung, brain, and intestine. Biochemical and molecular biological techniques are used to identify and characterize genetic and environmental factors that interact to produce adverse side effects of drugs.
The chemical, cellular, and molecular mechanisms by which chemicals in cigarette smoke or nanoparticles present in air damage lung tissues receive a particularly strong research prominence in the Department. In addition, nanoparticle-mediated adverse effects on vascular endothelial or intestinal cells are robust research areas. The results of these research projects may lead to a better understanding of environmentally induced lung, cardiovascular, and gastrointestinal diseases, and provide insights to design drugs to prevent toxicities to these organ systems.
There are numerous examples and opportunities within the Department for collaborative, interdisciplinary research. Faculty with primary research interests in drug metabolism and biochemical toxicology collaborate extensively, both within the Department and with others in the Health Sciences Center. A lively Toxicology Journal Club runs all year, and provides opportunities for faculty and graduate students to review and discuss the latest research developments.