Mentoring patient-oriented research in deep phenotyping of cardiac function for heart failure prevention

Amil Shah博士是哈佛医学院的医学副教授， 布里格姆妇女医院（BWH）的心脏病学家和心血管成像师。他的职业目标是 为心力衰竭（HF）的诊断、治疗和预防做出了重大贡献， 特别是射血分数保留（HFpEF）-通过有影响力的研究和有效的指导 下一代的调查员。他开发了一个成功的，独立的以患者为导向的研究（POR） 旨在通过将心脏成像整合到 前瞻性医院生理学研究、多中心流行病学队列和随机临床研究 审判他领导了有影响力的出版物，为HFpEF的病理生理学、诊断和管理提供信息， 获得了持续的NIH资助（PI在2个活跃的R 01赠款上）。他是22名学员的主要导师 迄今为止，他的计划提供了一个独特的平台，在POR的培训，这是放大的整合， 哈佛CTSA、BWH心血管成像T32项目和临床医学学位授予项目 在哈佛医学院和公共卫生学院的调查。他对K24提案的目标是 (1)通过参与教学和同行领导的研讨会来提高他的指导质量和范围;（2） 扩大他的研究计划，包括“组学”科学;（3）发展在分析高， 与成像表型和临床结果相关的三维“组学”数据。受K24保护的时间 将使沙阿博士能够在指导方面进行教学和同行领导的培训，扩大他的指导活动， 并参与“组学”科学的课程和“实践”培训。K24的资金将支持 他的研究计划扩展到翻译蛋白质组学和基因组学，包括计算 生物学支持HFpEF是常见的、病态的，并且患病率增加，但没有有效的疾病特异性 治疗目前存在。虽然HF pEF基础上的LV功能障碍是研究的重点， 已知的生物学途径促进在面对有害的心脏功能的保护， 合并症（心脏弹性）。这是一个重要的错失机会，无法制定干预措施， 正常的心脏功能，以防止HF。这项建议的具体科学目的是定义循环 个体蛋白质和蛋白质网络（1）与运动呈正相关和负相关， HFpEF特征性血流动力学扰动;（2）与晚年心脏弹性相关;（3） 最有可能是心脏弹性的介质，基于使用基因组数据的研究。目标1将发生在 在BWH前瞻性入组的患者接受有创运动试验。目标2和3将在 社区人群中的动脉粥样硬化风险，在杰克逊心脏研究中进行复制。合成 这些“组学”方法与他现有的研究计划将独特地定位沙阿博士垂直 促进对HFpEF病理生物学的理解，同时为他的学员提供丰富的POR培训机会。

Dr Amil Shah is an Associate Professor of Medicine at Harvard Medical School and an active clinical cardiologist and cardiovascular imager at Brigham and Women's Hospital (BWH). His overall career goal is to make substantial contributions to the diagnosis, treatment, and prevention of heart failure (HF) – and HF with preserved ejection fraction (HFpEF) in particular – through impactful research and effective mentoring of the next generation of investigators. He has developed a successful, independent patient oriented research (POR) program aiming to define the cardiac perturbations responsible for HFpEF by integrating cardiac imaging into prospective hospital-based physiologic studies, multicenter epidemiologic cohorts, and randomized clinical trials. He has led impactful publications informing HFpEF pathophysiology, diagnosis, and management, and has secured continuous NIH funding (PI on 2 active R01 grants). He has been primary mentor to 22 trainees to-date, and his program provides a unique platform for training in POR which is amplified by integration with the Harvard CTSA, BWH cardiovascular imaging T32 program, and degree-granting programs in clinical investigation at Harvard Medical School and School of Public Health. His objectives for this K24 proposal are (1) to improve the quality and scope of his mentoring by engaging in didactic and peer-led workshops; (2) to expand his research program to include `-omic' science; and (3) to develop expertise in analysis of high- dimensional `-omic' data to relate to imaging phenotypes and clinical outcomes. Protected time from the K24 will enable Dr Shah to pursue didactic and peer-led training in mentoring, to expand his mentoring activities, and to engage in coursework and `hands-on' training in `-omic' science. Funds from the K24 will support expansion of his research program into translational proteomics and genomics, including computational biology support. HFpEF is common, morbid, and increasing in prevalence, but no efficacious disease-specific therapy currently exists. While LV dysfunction underlying HFpEF is an intense focus of investigation, little is known regarding biological pathways promoting the preservation of cardiac function in the face of detrimental co-morbidities (cardiac resilience). This is a critical missed opportunity to develop interventions promoting normal cardiac function to prevent HF. The specific scientific aims of this proposal are to define circulating individual proteins and protein networks that (1) positively and negatively correlate with exercise- hemodynamic perturbations characteristic of HFpEF; (2) associate with cardiac resilience in late life; and (3) are most likely to be mediators of cardiac resilience based on studies using genomic data. Aim 1 will occur in patients prospectively enrolled at BWH to undergo invasive exercise testing. Aims 2 and 3 will be performed in the Atherosclerosis Risk in Communities cohort, with replication in the Jackson Heart Study. Synthesizing these `-omic' approaches with his existing research program will uniquely position Dr Shah to vertically advance understanding of HFpEF pathobiology, while enriching training opportunities in POR for his mentees.