Mentored Patient Oriented Research in Cardiometabolic Disease

Reilly博士在宾夕法尼亚大学（Penn）拥有独特的机械患者导向研究（POR）和指导记录。他的心脏代谢研究项目致力于动脉粥样硬化性心血管疾病（ASCVD）及其危险因素的人类转化和基因组研究。他的项目以宾夕法尼亚大学心血管和转化研究所为基础，并高度整合到宾夕法尼亚大学临床和转化科学奖赞助的培训任务中。这为翻译POR和指导K24学员提供了一个出色的环境。他拥有连续的NIH资助记录，在翻译POR方面的多名内科科学家的指导，以及由十几名受训者领导的许多高影响力的翻译出版物，其中一些人已经建立了自己独立的POR职业。Reilly博士认识到将基础科学和尖端转化技术纳入POR学术生涯的挑战。他致力于用这些方法培训年轻的临床研究者，并指导他们在POR中独立发展。在这个申请中，他提出(1)提高他的科学和指导技能，投入更多的时间在机械POR上；(2)增加时间和结构，指导新的临床研究者进行机械POR；(3)追求新的创新POR，为指导年轻的临床研究者提供独特的培训环境和POR框架。尽管最近的基因组发现已经确定了与ASCVD及其危险因素的新关联，但关键的挑战仍然是如何证明这些基因座是如何导致疾病的，以及如何在临床应用和治疗靶向方面取得进展。拟议的K24研究将招募健康的人，从脂肪组织活检中产生诱导多能干细胞（iPS）。这些iPS细胞将用于进行初步研究，研究最近发现的心脏病的组织特异性功能，(a) SORT1，一种新的ldl -胆固醇和心肌梗死基因座，用于调节肝细胞脂蛋白，(b) ABO，一种风险内皮生物标志物和心肌梗死基因座，用于调节内皮分泌蛋白。Reilly博士将通过减少行政和临床职责，将40%的精力用于K24提案（5%用于增强他的指导和POR技能；10%用于研究提案；25%用于指导新的研究人员）。K24奖提供了理想的机制，以扩大他的机械性POR项目，同时致力于培养年轻的临床研究者。

DESCRIPTION (provided by applicant): Project Summary Dr. Reilly has a track record in unique mechanistic patient oriented research (POR) and mentorship at the University of Pennsylvania (Penn). His Cardiometabolic Research Program is dedicated to human translational and genomic studies of atherosclerotic cardiovascular disease (ASCVD) and its risk factors. His program is based in Penn's Cardiovascular and Translational Institutes and highly integrated into the training missions sponsored by Penn's Clinical and Translational Science Award. This provides an outstanding environment for translational POR and for mentoring K24 trainees. He has had a track record of continuous NIH funding, mentorship of multiple physician scientists in translational POR, and numerous high-impact translational publications led by over a dozen trainees, several of whom have established their own independent POR careers. Dr Reilly recognizes the challenges to incorporating basic science and cutting edge translational technologies into academic careers in POR. He is committed to training young clinical investigators in these approaches and mentoring them to independent careers in POR. In this application, he proposes to (1) augment his scientific and mentoring skills and devote more time to mechanistic POR, (2) provide increased time and structure in mentoring new clinical investigators in the conduct of mechanistic POR, and (3) pursue new innovative POR in order to provide a unique training environment and POR framework for mentoring young clinical investigators. Although recent genomic discoveries have identified novel associations with ASCVD and its risk factors, the key challenge remains in demonstrating how these loci cause disease and can be advanced for clinical application and therapeutic targeting. The proposed K24 research will recruit healthy humans to generate induced pluripotent stem (iPS) cells from adipose tissue biopsies. The iPS cells will be used to address pilot studies tissue-specific functional studies of recent genomic discoveries for heart disease, (a) SORT1, a novel LDL-cholesterol and myocardial infarction locus, in regulation of hepatocyte lipoproteins and, (b) ABO, a locus for risk endothelial risk biomarkers and myocardial infarction, in regulation of endothelial secreted proteins. Dr Reilly will dedicate 40% effort to this K24 proposal (5% to augment his mentorship and POR skills; 10% to the research proposal; and 25% to mentoring new investigators) through reduction in administrative and clinical duties. The K24 award provides the ideal mechanism to expand his mechanistic POR program while simultaneously dedicating significant effort to train young clinical investigators. PUBLIC HEALTH RELEVANCE: Project Narrative Dr. Reilly has a track record in unique mechanistic patient oriented research (POR) and mentorship at the University of Pennsylvania. His Cardiometabolic Research Program is dedicated to translational and genomic studies of human atherosclerosis and its risk factors. In this application, he proposes to (1) augment his scientific and mentoring skills and devote more time to mechanistic POR, (2) provide increased time and structure in mentoring new clinical investigators in the conduct of mechanistic POR, and (3) pursue new innovative POR in order to generate a unique training environment and POR framework for mentoring young clinical investigators.