An Integrated Approach to Personalized Medicine

描述（由申请人提供）：这是Andrew a . Monte博士为药物基因组学和个性化医学转化学者职业奖（K23）提交的一份新材料。Monte博士的总体职业目标是成为个性化医学领域的领先独立研究员。他的创新研究计划整合了临床、基因组、细胞色素代谢表型和代谢组学因素，以开发一个预测美托洛尔引起的收缩压下降的模型。候选人：Monte博士是一名委员会认证的急诊医学和医学毒理学医生，科罗拉多大学丹佛分校（UCD）医学院和斯卡格斯药学院的急诊医学和医学毒理学助理教授。培训：拟议的职业发展计划增加了Monte博士之前的培训和经验，专注于具体的高级培训：(1)药物基因组学方法；(2)药代动力学分析；(3)代谢组学分析；(4)建立预测模型。蒙特博士建议通过集中的指导、相关的高级课程和指导性研究来获得这些技能。这些培训活动将帮助蒙特博士获得必要的技能，成为个性化医疗的领导者。导师/环境：Monte博士与他的主要导师Vasilis Vasiliou博士建立了密切的工作关系，Vasilis Vasiliou博士是基因组学领域的领先研究员，有着长期的指导记录。他的共同导师Richard M. Weinshilboum博士是药物代谢酶方面的国家专家和研究员。此外，一个由药代动力学、代谢组学、模型构建和研究职业发展专家组成的顾问小组将监督Monte博士的进展，并提供额外的局部指导。急诊医学系致力于支持蒙特博士成长为一名独立的研究人员，包括承诺为该职业发展奖提供受保护的时间和资源。此外，UCD为Monte博士提供了丰富的研究环境，包括访问CCTSI的资源和合作者。研究：Monte博士的研究计划收集临床、基因组（Aim 1）、细胞色素（CYP）代谢表型（Aim 2）和代谢组学数据（Aim 3），对一名开始美托洛尔治疗不受控制的高血压的患者进行前瞻性试验。将这些因素进行比较，以确定哪些变量可以预测对美托洛尔的药物反应。这些数据将整合到一个模型中，以预测美托洛尔导致的收缩压降低。摘要：这种创新的方法整合了临床、基因组、CYP代谢表型和代谢组学数据来预测美托洛尔的药物反应。该综合方法可应用于其他疾病和治疗，以提高药物疗效和安全性。培训计划和研究计划将帮助Dr. Monte发展成为国际公认的个性化医疗独立研究者。

DESCRIPTION (provided by applicant): This is a new submission for the Translational Scholar Career Awards in Pharmacogenomics and Personalized medicine (K23) for Andrew A. Monte, MD. Dr. Monte's overall career goal is to become a leading independent researcher in personalized medicine. His innovative research proposal integrates clinical, genomic, cytochrome metabolism phenotype, and metabolomic factors to develop a model that predicts systolic blood pressure decline due to metoprolol. Candidate: Dr. Monte is a board-certified Emergency Medicine & Medical Toxicology physician, Assistant Professor of Emergency Medicine & Medical Toxicology at the University of Colorado Denver (UCD) School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. Training: The proposed career development plan augments Dr. Monte's prior training and experience to focus on specific, advanced training in: (1) pharmacogenomics methods; (2) pharmacokinetic analyses; (3) metabolomic analyses; and (4) predictive model building. Dr. Monte proposes to acquire these skills through intensive focused mentorship, relevant advanced coursework, and guided research. These training activities will help Dr. Monte gain the necessary skills to become a leader in personalized medicine. Mentors/Environment: Dr. Monte has established a close working relationship with his primary mentor, Dr. Vasilis Vasiliou, a leading researcher in genomics with a long track record of mentoring. His co-mentor, Dr. Richard M. Weinshilboum, is a national expert and researcher on drug metabolizing enzymes. In addition, an advisory panel of experts in pharmacokinetics, metabolomics, model building, and research career development will monitor Dr. Monte's progress and providing additional topical guidance. The Department of Emergency Medicine is committed to supporting Dr. Monte's growth into an independent researcher, including a commitment of protected time and resources for this career development award. In addition, UCD provides Dr. Monte with a rich research environment, including access to resources and collaborators at the CCTSI. Research: Dr. Monte's research proposal gathers clinical, genomic (Aim 1), cytochrome (CYP) metabolism phenotype (Aim 2), and metabolomic data (Aim 3) in a prospective trial of a patients beginning metoprolol therapy for uncontrolled hypertension. These factors will be compared to identify which variables predict the drug response to metoprolol. These data will be integrated into a model to predict systolic blood pressure reduction due to metoprolol. Summary: This innovative approach integrates clinical, genomic, CYP metabolism phenotype, and metabolomic data to predict the drug response of metoprolol. The integrative approach can be applied to other diseases and therapeutics to improve drug efficacy and safety. The training plan and research proposal will help Dr. Monte develop into an internationally-recognized independent investigator in personalized medicine.