An Integrated Approach to Personalized Medicine

个性化医疗的综合方法

• 批准号: 8914016
• 负责人: Andrew Albert Monte
• 金额: $ 19.6万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914016
• 关键词: Accounting; Adrenergic Receptor; Adverse drug effect; Affect; Age Factors; Award; Binding; Blood Pressure; Body mass index; CYP2D6 gene; Chronic; Chronic Disease; Clinical; Clinical Data; Clinical Trials; Colorado; Complex; Cytochromes; Data; Development; Development Plans; Dextromethorphan; Disease; Dose; Drug Interactions; Drug Kinetics; Drug Prescriptions; Drug Targeting; Drug effect disorder; Drug usage; Emergency Medicine; Environment; Enzymes; Ethnic Origin; Explosion; Genetic; Genetic Variation; Genomics; Genotype; Goals; Growth; Health; Hypertension; Ingestion; K-Series Research Career Programs; Knowledge; Logistic Regressions; Measurement; Medical; Mentors; Mentorship; Metabolic; Metabolism; Methods; Metoprolol; Modeling; Monitor; Patient Rights; Patients; Pattern; Pharmaceutical Preparations; Pharmacogenomics; Pharmacologic Substance; Pharmacy Schools; Phenotype; Physician Assistants; Population Heterogeneity; Race; Receptors, Adrenergic, beta-1; Relative (related person); Research; Research Personnel; Research Proposals; Resources; Safety; Science; Site; Therapeutic; Time; Titrations; Toxicology; Training; Training Activity; Treatment Efficacy; Universities; Urine; Work; absorption; base; blood pressure reduction; blood pressure regulation; career; career development; drug clearance; drug efficacy; drug metabolism; experience; hypertension treatment; improved; innovation; medical schools; meetings; metabolomics; model building; personalized medicine; predictive modeling; professor; prospective; response; sex; skills; small molecule; success

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.

描述(由申请人提供)：这是为安德鲁·A·蒙特，医学博士提供的药物基因组学和个性化医学翻译学者职业生涯奖(K23)的新提交。蒙特博士的总体职业目标是成为个性化医学领域领先的独立研究人员。他的创新研究方案整合了临床、基因组、细胞色素代谢表型和代谢因素，开发了一个预测美托洛尔引起的收缩压下降的模型。候选人：蒙特博士是科罗拉多大学丹佛分校(UCD)医学院和斯卡格斯药学与药学学院的急诊医学和医学毒理学助理教授，董事会认证的急诊医学和医学毒理学医生。培训：拟议的职业发展计划加强了蒙特博士先前的培训和经验，侧重于以下方面的具体高级培训：(1)药物基因组学方法；(2)药代动力学分析；(3)新陈代谢分析；以及(4)预测模型建立。蒙特博士建议通过密集而专注的指导、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，成为个性化医疗领域的领导者。导师/环境：蒙特博士与他的主要导师瓦西里斯·瓦西利乌博士建立了密切的工作关系，瓦西里斯·瓦西利乌博士是基因组学领域的领军人物，有长期的指导记录。他的合作导师理查德·M·温希尔布姆博士是药物代谢酶方面的全国性专家和研究人员。此外，一个由药代动力学、新陈代谢组学、模型建立和研究事业发展方面的专家组成的顾问小组将监督蒙特博士的进展，并提供额外的局部指导。急诊医学部致力于支持蒙特博士成长为一名独立研究人员，包括承诺为这一职业发展奖提供受保护的时间和资源。此外，UCD为蒙特特博士提供了丰富的研究环境，包括获得CCTSI的资源和合作者。研究：蒙特博士的研究提案收集了临床、基因组(AIM 1)、细胞色素(CYP)代谢表型(AIM 2)和代谢组数据(AIM 3)，这是一项对一名开始接受美托洛尔治疗失控高血压患者的前瞻性试验。这些因素将进行比较，以确定哪些变量可以预测美托洛尔的药物反应。这些数据将被整合到一个模型中，以预测美托洛尔导致的收缩压下降。摘要：这一创新的方法综合了临床、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，以提高药物的疗效和安全性。培训计划和研究提案将帮助蒙特博士发展成为国际公认的个性化医学独立研究员。