Hormone mediated mechanisms of altered drug metabolism and transport in transgender adults

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PROJECT SUMMARY/ABSTRACT Dr. Lauren Cirrincione, an Assistant Professor at the University of Washington School of Pharmacy, is applying for a K23 award. She completed a PharmD and clinical HIV pharmacology fellowship, and she is a tenure- eligible faculty member at the University of Washington School of Pharmacy. She is awarded a start-up package and 9-person months of protected time and is working to establish herself as a clinical translational investigator in clinical pharmacology of transgender medicine. 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 K23 grant will provide: (1) expertise in probe substrate study methods and analysis and (2) longitudinal study design in transgender adults and (3) training in skills needed to become an independent NIH-funded investigator with expertise in hormone mediated mechanisms of altered drug disposition. To achieve these goals, Dr. Cirrincione's mentorship and research team consists of internationally recognized experts in clinical pharmacology, endocrinology, and statistics who will support the proposed training plan and research proposal. All faculty mentors have a strong track record of mentorship, know Dr. Cirrincione well, have established collaborative research programs, and will assist Dr. Cirrincione in career development. Training and research will occur at the University of Washington, a global leader in research and strong environment to support early career investigators develop into independently funded investigators. This proposal addresses an important gap in transgender medicine, specifically whether high-dose sex hormone therapy alters the disposition of other prescribed drugs. We propose to study 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.