Discovery, Implementation and Mentorship in Personalized Cardiovascular Pharmacotherapy

摘要 我建立了一个成功的以病人为导向的研究项目，专注于药物基因组学， 药物流行病学和慢性病流行病学，重点是心血管疾病。我 研究的目的是阐明临床、环境和遗传因素对 心血管疾病的风险和对药物的反应，并使用这些信息来定制治疗， 尤其是在有多种合并症的患者中。 拟议中的奖励将使我能够继续指导，同时扩大我的研究计划 特别是纳入实施科学工具，以解决关键的转化知识差距。的 本文提出的新研究是建立在正在进行的工作，以创造独特的和急需的病人 心血管药物治疗学的面向研究（POR）培训机会， 通过整合基因组信息进行风险预测。我的国家卫生研究院赠款沿着的四个新项目将 形成学员（医学博士、药学博士和博士）培训的基础。导师制旨在扩大POR培训 实习生的机会。学员将领导新项目，发展与发现相关的技能， 执行、进行分析和发表原创研究。他们将利用这一点提出新的 研究作为其NIH-K23应用的一部分。 项目1将阐明性别和年龄对基因-出血关联的不同影响， 抗凝剂使用者。项目2将评价药物遗传学变体对阿哌沙班的影响， 利伐沙班药代动力学和药效学。项目3将评估 急性冠脉综合征患者出血风险评分和遗传学风险预测 急性冠脉综合征（ACS）患者接受经皮冠状动脉介入治疗（PCI）。项目4将评估 心力衰竭对接受PCI的ACS患者预后的影响 在UAB的支持和协作环境中，这个奖项将确保我继续成长。 研究计划扩展到包括混合实施有效性设计和建立POR能力 通过指导初级调查员建立自己的职业生涯。多个NIH的广度和深度- 资助的机构培训计划，UAB的CTSA和她在UAB的翻译领导 药物基因组学和精准医学研究所将提供资源和基础， 推进发现和实施工作，使研究发现转化为临床 在乎

Abstract I have built a successful patient oriented research program focused on pharmacogenomics, pharmacoepidemiology, and chronic disease epidemiology with a focus on cardiovascular diseases. My research goal is to elucidate the role of clinical, environmental and genetic factors on variability in cardiovascular disease risk and response to medications and to use this information to tailor treatments, especially in patients with multiple comorbidities. The proposed award would enable me to continue mentoring while expanding my research program specifically incorporating implementation science tools to address key translational knowledge gaps. The new research proposed herein is builds on ongoing work to create unique and much needed patient oriented research (POR) training opportunities in cardiovascular pharmacotherapeutics and improvement in risk prediction by incorporating genomic information. My NIH grants along with the four new projects will form the basis for the mentee (MD, Pharm.D, and PhD) training. Mentorship aims expand the POR training opportunities for trainees. Mentees will lead the new projects, develop skills related to discovery and implementation, conduct analysis and publish original research. They will leverage this to propose new research as part of their NIH- K23 applications. PROJECT1 will elucidate the differential effect of sex and age on gene-hemorrhage association among anticoagulant users. PROJECT 2 will evaluate the influence of pharmacogenetic variants on Apixaban and Rivaroxaban pharmacokinetics and pharmacodynamics. PROJECT 3 will evaluate the performance of bleeding risk scores and the integration of genetics in risk prediction among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). PROJECT 4 will evaluate the influence of heart failure on outcomes among patients with ACS undergoing PCI. In the supportive and collaborative environment of UAB, this award will ensure that I continue to grow my research program expand to include hybrid implementation-effectiveness designs and build capacity in POR by mentoring junior investigators to build their own careers. The breadth and depth of the multiple NIH- funded institutional training programs, UAB’s CTSA and her leadership in UAB’s Translational Pharmacogenomics and Precision Medicine Institute will provide the resources and the foundation to advance discovery and implementation efforts to enable translation of research discoveries into clinical care.