Department of Pharmacology and Toxicology
B.S., University of Wisconsin-Milwaukee
Faculty Advisor: Dr. D. Gail McCarver
Phone: (414) 955-4187
My research focuses on the expression of hepatic phase I drug metabolizing enzymes, particularly cytochromes P450 CYP3A4 and 3A7 and two flavin-containing monooxygenases (FMO), FMO1 and FMO3. These enzymes exhibit a temporal specific expression pattern during human development. Throughout fetal development, CYP3A7 is expressed at its highest levels whereas CYP3A4 is present at very low levels; after birth, there is an inversion of this expression pattern. Within one to two years, CYP3A7 expression is eliminated while CYP3A4 levels increase to become the predominant cytochrome P450. A similar inverse expression pattern is observed between fetal expressed FMO1 and adult expressed FMO3. For both gene families, there is considerable interindividual variation with regards to the timing of this transition, leading to highly variable drug metabolism capacity during this critical window of development. Current studies are elucidating the underlying mechanisms responsible for temporal-dependent transition between these genes. Understanding these mechanisms will further advance our knowledge of age-specific xenobiotic disposition, as well as allow an initial exploration of mechanisms underlying interindividual variability.