Sheena Sharma is the Drug Metabolism and Disposition Highlighted Trainee Author for the December 2022 issue. She is a Ph.D. candidate in Dr. Bhagwat Prasad’s laboratory at the College of Pharmacy and Pharmaceutical Sciences, Washington State University. The DMD article that earned her selection as a Highlighted Trainee Author is titled "Dimethandrolone (DMA), a Potential Male Contraceptive Pill, is Primarily Metabolized by the Highly Polymorphic UGT2B17 Enzyme in Human Intestine and Liver" and is available at https://doi.org/10.1124/dmd.122.001041.
Mrs. Sharma’s primary research area is prediction of drug pharmacokinetics (PK) using a combination of in vitro assays, in vivo preclinical or clinical studies, and physiologically based PK (PBPK) modeling. Her current work is focused on developing a mechanistic understanding of the effect of physiological, drug-related, and environmental factors on the PK of orally absorbed drugs. The identification of risk factors (e.g., genetic polymorphism) associated with variability in drug absorption will allow reliable predictions of drug concentrations by integration into proteomics-informed PBPK models.
Her research project is to characterize mechanisms leading to poor and variable oral bioavailability of DMA, an oral investigational male hormonal contraceptive. DMA undecanoate (DMAU), which is hydrolyzed to DMA in vivo, has been shown to be an effective, reversible contraceptive when dosed orally in pre-clinical studies. However, factors associated with variability in serum DMA levels are not well characterized. Mrs. Sharma identified that the highly polymorphic UDP-glucuronosyltransferase 2B17 (UGT2B17) enzyme plays a major role in the first-pass metabolism of DMA, which is likely the key mechanism of variable DMA bioavailability.
The anticipated impact of Mrs. Sharma’s research is the consideration of UGT2B17-mediated first-pass metabolism in designing a safe and effective oral DMAU delivery. To do so, subjects can be stratified into null-, mid-, and high-expressors of UGT2B17 for achieving less variable and potentially safer clinical trials.
When not in the lab, Sheena enjoys cooking, reading, and jogging.