The focus of our lab is conjugative metabolism of xenobiotics. Metabolism of drugs is a critical factor affecting their pharmacokinetic behavior. Metabolism can lead to both inactivation and activation of drugs. ‘Phase II’ or conjugative metabolism is catalyzed by several enzyme families. Our research focus is two enzyme superfamilies: the uridine diphosphoglucuronosyltransferases (UGTs) and cytosolic sulfotransferases (SULTs). Family members of these enzyme families are known to exhibit genetic variability. The role of UGT and SULT pharmacogenetics in altered xenobiotic disposition is an area of strong interest.

Current Projects

Cancer prevention: role of conjugative metabolism

This project focuses on cancer chemoprevention. Colorectal and breast cancer risk and incidence are affected both by a person’s genetics and environmental exposure. Dietary polyphenols naturally found in vegetables and fruits have potential as cancer chemopreventives. One such chemical currently being evaluated is resveratrol. Resveratrol is extensively sulfated and glucuronidated in the human body. The kinetics of resveratrol metabolism, cellular effects, genotype – phenotype correlations, and drug-drug interactions are areas of inquiry in our lab.

Gastroparesis: drug-drug interactions and pharmacogenetics of DMEs

This project is in collaboration with Dr. Henry Parkman, Temple University School of Medicine. Several drugs co-administered for the management of gastroparesis are metabolized via common drug metabolizing enzymes (DMEs). Drug-drug interactions are being characterized in vitro, and their potential for a clinical pharmacokinetic / pharmacodynamic interaction is additionally evaluated. For drugs metabolized by genetically polymorphic enzymes, the correlation between observed patient variability in drug response and the patient’s genetic make-up will be studied.