Dr. Lauren Cirrincione, an Assistant Professor at the University of Washington School of Pharmacy, is applying for a K23 award. Dr. Cirrincione’s career goals include making significant contributions to the field of hormone mediated drug interactions in transgender and gender diverse adults, specifically applying clinical pharmacology to transgender medicine. This grant will provide 1. expertise in probe substrate study methods and analysis and 2. longitudinal study design and 3. training to become an independent NIH-funded investigator with expertise in hormone mediated mechanisms of altered drug disposition and will address whether high-dose sex hormone therapy alters the disposition of other prescribed drugs. We will use a probe substrate-biomarker-protein activity framework to test differences in major drug handling proteins before and during estradiol treatment in vivo. Dr. Cirrincione will gain expertise in conducting mechanistic, clinical pharmacology studies in transgender adults. Data generated from this proposal will be used to advance clinical strategies to overcome changes in drug safety and efficacy in transgender adults and to increase available in vivo mechanistic data to establish the role of sex hormones on pathways of drug disposition.