- Ph.D. - 1996 University of Texas, Graduate School of Biomedical Sciences, Houston, Texas
My laboratory is interested in basic regulatory mechanisms in toxicology and drug disposition. We work primarily with mice and tissue culture as model systems to investigate two major questions. (1) What role do hepatic ligand-activated transcription factors play in regulating drug disposition? (2) How do alterations in either nutritional- or health-status impact drug disposition?
All organisms are exposed to foreign compounds, or xenobiotics, which include naturally occurring compounds such as alkaloids, plant metabolites, pyrolysis products in cooked food, and toxins, as well as man-made compounds including drugs, industrial pollutants, and pesticides. The metabolic process of converting these compounds from being lipid-soluble to water-soluble is referred to as biotransformation. The resulting water-soluble compounds are eventually disposed of in urine or feces.
Some compounds accelerate their own metabolism in liver by inducing transcription of genes that function in biotransformation. Cytochrome P450 3A (CYP3A) is the major hepatic enzyme responsible for metabolism of approximately 60% of all clinically prescribed drugs, and induction of CYP3A occurs through the pregnane-X-receptor (PXR).
One focus of our laboratory is to identify novel PXR-target genes as well as PXR-activating ligands using gene-array and real-time PCR methods together with a PXR-gene knockout mouse model. Another focus of our laboratory is to determine the extent to which caloric restriction and inflammation impact drug disposition through alterations in hepatic ligand-activated transcription factor complexes.
Students in our lab learn techniques in molecular biology, biochemistry, and pharmacology that address fundamental questions regarding the biology of xenobiotic and drug disposition.