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

项目概要/摘要 博士华盛顿大学药学院助理教授劳伦·奇林乔内正在申请 获得K23奖。她完成了药学博士和临床艾滋病毒药理学奖学金，她是一个终身职位- 华盛顿大学药学院的合格教员。她被授予了一个创业 包和9人月的保护时间，并正在努力建立自己作为一个临床翻译 跨性别医学临床药理学研究者。Cirrincione博士的职业目标包括 对跨性别和性别多样性中激素介导的药物相互作用领域的重大贡献 成人，特别是将临床药理学应用于跨性别医学。K23将提供：（1） 探针底物研究方法和分析方面的专业知识，以及（2）跨性别纵向研究设计 成年人和（3）成为独立的NIH资助的研究者所需的技能培训， 激素介导的药物处置改变的机制。为了实现这些目标，Cirrincione博士 导师和研究团队由国际公认的临床药理学专家组成， 内分泌学和统计学，谁将支持拟议的培训计划和研究建议。所有教职 导师有很好的指导记录，很好地了解Cirrincione博士，已经建立了合作关系， 研究计划，并将协助Cirrincione博士的职业发展。培训和研究将在 华盛顿大学，在研究和强大的环境，以支持早期职业生涯的全球领导者 调查员发展成为独立供资的调查员。该提案解决了以下方面的一个重要差距： 跨性别医学，特别是高剂量的性激素治疗是否会改变其他人的性格， 处方药我们建议研究一个探针底物→生物标志物→蛋白活性的框架来测试 体内雌二醇治疗前和治疗期间主要药物处理蛋白的差异。Cirrincione博士将 获得在变性成年人中进行机械，临床药理学研究的专业知识。生成的数据 将用于推进临床策略，以克服药物安全性和有效性的变化 在变性成年人中，并增加可用的体内机制数据，以确定性激素的作用 药物处置的途径。

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.