Patient Oriented Research in Cardiovascular Regeneration

 描述（由申请人提供）：这是一个重新提交的K24中期职业研究者奖在以患者为导向的研究（POR）。申请人菲利普杨博士是斯坦福大学的医学科学家和医学（心血管医学）副教授。在过去的10年里，杨博士在分子/细胞成像和干细胞生物学的交叉点上发展了跨学科的翻译专业知识。他巩固了他的专业知识，在再生医学的POR培训，发展独立的POR职业生涯，并指导初级临床研究人员。为了实现这一目标，他获得了NIH，AHA和CIRM与干细胞临床应用相关的独立研究奖。最值得注意的是，他获得了NIH/NHLBI UM 1心血管细胞治疗研究网络（CCTRN）的资助，这是一项为期7年（2012- 2019）的7300万美元的工作，由7个学术网站组成，用于设计新型细胞治疗的多中心临床试验。CCTRN将提供进行POR和指导初级临床研究者的总体框架。杨博士在斯坦福大学领导进行CCTRN赞助的母公司临床试验，c- kit细胞和间充质细胞的组合：一种新型的双细胞研究，评估慢性心力衰竭治疗的再生特性（CONCERT）。CONCERT是一项多中心、随机、双盲临床试验，旨在研究3种干细胞群在144例缺血性心肌病患者中的作用：1）间充质干细胞（MSC），2）ckit+心脏祖细胞干细胞（CPC），3）联合MSC/CSC，4）安慰剂。CCTRN UM 1奖每年为POR提供350，000美元的直接费用，以及举办音乐会的费用。K24旨在利用CONCERT的资源和基础设施，为Yang博士提供宝贵的机会，以增强其POR并指导初级研究者。除了进行CONCERT试验外，Yang博士还将招募CONCERT患者进行两项辅助研究，以研究锰增强MRI（MEMRI）和iPSC衍生心肌细胞（iCM）的临床效用。MEMRI研究将评估细胞治疗对梗死周围区域（PIR）的直接影响。MEMRI数据将与临床结果相关联，以确定实时可视化干细胞直接治疗效果的能力。iCM研究将评估患者特异性iCM对细胞治疗的直接体外反应。患者特异性iCM的功能测定将提供对细胞疗法的个体应答的高分辨率评估，并可能与MEMRI相关。K24提案将为Yang博士的25% FTE提供支持，并为MEMRI和iCM研究提供物资。杨博士有超过10年的指导初级临床科学家，博士后研究员，医学生，研究生和本科生的历史-所有执行POR。这笔资金将提供受保护的时间，以加强和提高杨博士正在进行的POR和指导新的临床研究者。

 DESCRIPTION (provided by applicant): This is a resubmission for the K24 Midcareer Investigator Award in Patient-Oriented Research (POR). The applicant, Dr. Phillip Yang, is a physician-scientist and Associate Professor of Medicine (Cardiovascular Medicine) at Stanford University. Over the past 10 years, Dr. Yang has developed an interdisciplinary translational expertise at the intersection of molecular/cellular imaging and stem cell biology. He has consolidated his expertise to train in POR in regenerative medicine, develop an independent POR career, and mentor the junior clinical investigators. To accomplish this objective, he has received independent research awards from the NIH, AHA, and CIRM related to clinical application of stem cells. Most notably, he received the NIH/NHLBI UM1 Cardiovascular Cell Therapy Research Network (CCTRN) grant, which is a 7-year (2012- 2019) $73M effort, consisting of 7 academic sites to design multi-center clinical trials of novel cell therapy. CCTRN will provide the overall framework to conduct POR and to mentor junior clinical investigators. Dr. Yang leads the effort at Stanford to conduct the CCTRN sponsored parent clinical trial, Combination Of c- kit cells and mesenchymal cells: a Novel, dual Cell study Evaluating Regenerative properties for Treatment in Chronic Heart Failure (CONCERT). CONCERT is a multi-center, randomized, double-blinded clinical trial designed to study the effects of 3 stem cel populations in 144 ischemic cardiomyopathy patients: 1) mesenchymal stem cells (MSCs), 2) ckit+ cardiac progenitor stem cells (CPCs), 3) combined MSC/CSCs, and 4) placebo. The CCTRN UM1 Award provides $350,000 per year in direct costs for POR in addition to the cost of conducting CONCERT. This K24 is designed to leverage the resource and infrastructure of CONCERT to allow an invaluable opportunity for Dr. Yang to augment his POR and mentor the junior investigators. In addition to conducting the CONCERT trial, Dr. Yang will recruit the CONCERT patients to undergo two ancillary studies to investigate the clinical utility of manganese-enhanced MRI (MEMRI) and iPSC-derived cardiomyocytes (iCMs). The MEMRI study will assess the direct effects of cell therapy on the peri-infarct region (PIR). The MEMRI data will be correlated with the clinical outcome to determine the ability to visualize the direct therapeutic effects of stem cells in real-time. The iCM study will assess the direct in vitro response of the patient-specific iCMs to cell therapy. Functional assays of the patient-specific iCMs will provide a high- resolution assessment of the individual response to cell therapy and potentially correlate with MEMRI. The K24 proposal will provide support for Dr. Yang's 25% FTE and supplies for MEMRI and iCM studies. Dr. Yang has over 10-year history of mentoring junior clinician scientists, postdoctoral fellows, medical students, graduate students, and undergraduates - all performing POR. This funding will provide protected time to augment and enhance Dr. Yang's ongoing POR and mentor new clinical investigators.