Investigators and Program Directors

Research Interests

The cytochrome P450 gene superfamily, because of the immensely broad substrate specificities of its gene products, is broadly implicated in drug and other xenobiotic metabolism and in the metabolism of many endogenous compounds including steroids, fatty acids, and retinoids. These metabolic activities make the cytochromes P450 (P450s) key players in toxicology, pharmacology, chemical carcinogenesis, and endocrinology. This laboratory is currently studying the function and regulation of the P450s, primarily human forms. Projects are focused on extrahepatic P450s - those expressed in the small intestine. We are investigating which forms, of the 57 currently identified in humans, are expressed in these tissues, how they function and how they are regulated. In the small intestine the potential of the P450s to affect the ultimate absorption of drugs and other xenobiotics through metabolism is being investigated. Current studies in the small intestine are centered on the role of a newly discovered P450 in rats in catalyzing the formation of retinoic acids from retinals (products of vitamin A). A comparable activity is being sought in human small intestine. The influence of P450 metabolism of drugs is now being probed by the developing technology of metabolomics. This approach, in which the changes in the flux of all of the endogenous metabolites is determined, shows tremendous potential. The long-term objectives of the studies are to gain insight into how the P450s function to enable preventative strategies to be developed against P450-associated toxicants and particularly environmental disease.

Contact Information

Phone: (518) 474-4920
Fax: 486-1505
E-mail: kaminsky@wadsworth.org.