META - Mentor, Educate, Train, Advocate: Patient Oriented Researchers in Cardiometabolic Disease

META - 导师、教育、培训、倡导：心脏代谢疾病领域以患者为导向的研究人员

• 批准号: 10320940
• 负责人: Latha P Palaniappan
• 金额: $ 11.82万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320940
• 关键词: Adult; Advocacy; Advocate; Affect; American; Area; Award; Cardiac; Cardiac Myocytes; Cardiometabolic Disease; Cardiovascular system; Career Mobility; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complex; Conduct Clinical Trials; Core Facility; Development Plans; Diabetes Mellitus; Educational process of instructing; Endothelial Cells; Enrollment; Environment; Etiology; Exhibits; Faculty; Functional disorder; Funding; Goals; Health; Health Services; Human; Individual; Institutes; Institution; Intervention; Knowledge; Lead; Medical; Medicine; Mentors; Mentorship; MicroRNAs; Mid-Career Clinical Scientist Award (K24); Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Output; Overweight; Participant; Pathway interactions; Patients; Persons; Phase; Physical activity; Population; Prevention; Randomized Clinical Trials; Regimen; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Research Training; Sampling; Science; Technology; Time; Training; Training and Education; Translating; United States; United States National Institutes of Health; Universities; Weight; Work; antiangiogenesis therapy; base; biobank; cardiometabolism; career; career development; diabetic; disorder prevention; exercise intervention; exosome; experience; field study; hepatic gluconeogenesis; induced pluripotent stem cell; innovation; interest; medical specialties; metabolomics; mortality; next generation; novel; obese person; patient oriented; patient oriented research; prevent; professor; programs; stem cells; strength training; translational scientist

PROJECT SUMMARY Dr. Latha Palaniappan, MD, MS is a well-recognized clinical researcher with a long track record of funding, expertise, and mentoring in patient-oriented research (POR) in cardiometabolic disease. As a newly-appointed Professor of Medicine at Stanford University, her extensive clinical research and teaching experience will help her mentor and train the next generation clinical and translational scientists in POR. Although Dr. Palaniappan is currently the lead investigator of two NIH-funded clinical trials, she is seeking support to pursue novel mechanistic research directions in cardiometabolic health, particularly in adults of normal weight with Type 2 diabetes, which affects over 3 million Americans and is associated with higher cardiovascular mortality. In addition, this K24 proposal will leverage Dr. Palaniappan’s breadth of experience to provide an innovative and dynamic setting to train mentees in POR. Her mentees can leverage the existing research platform available through two large, randomized clinical trials (RCTs), namely STRONG-D (normal weight) and IMPACT (overweight/obese), and an existing institutional biobank (Stanford GenePool). These biobanked samples will provide the basis for her future research direction which will focus on mechanistic differences in cardiometabolic health in three groups: normal-weight patients with diabetes (STRONG-D), overweight/obese (IMPACT) individuals with diabetes, and normal weight normoglycemic individuals (Stanford GenePool). She will use human induced pluripotent stem cells, metabolomics, and exosome profiling. The Specific Aims are as follows: Aim 1: Characterize cardiometabolic health across the three groups (n=40 in each group). We hypothesize that normal-weight people with diabetes (NWD) will be most cardiometabolically unhealthy followed by overweight/obese PWDs, followed by normal-weight normoglycemia. Aim 2: Investigate the functional differences in human induced pluripotent stem cells (iPSCs), specifically in cardiomyocytes and endothelial cells across the three groups (n=3 in each group). We hypothesize that individuals with normal weight diabetes will exhibit more dysfunction in cardiomyocytes (less cardiac contractility) and endothelial cells (less nitric oxide output). Aim 3: Examine metabolite profiles across the three groups (n=40 in each group). We hypothesize that NWDs will have more hepatic gluconeogenesis metabolites than overweight or obese individuals with diabetes. Aim 4: Evaluate and compare exosome profiles across the three groups (n=40 in each group). We hypothesize that NWDs will express more anti-angiogenesis miRNAs (miR-320) than overweight/obese individuals with diabetes after controlling for weight. This proposal will identify new pathways for intervention to predict, prevent and treat mortality and morbidity in normal weight diabetes.

项目摘要 MD，医学博士Latha Palaniappan博士是一位公认的临床研究人员，拥有悠久的资金记录， 专业知识和心脏代谢性疾病的患者研究（POR）的心理。作为新任命的 斯坦福大学医学教授，她的广泛临床研究和教学经验将有助于 她的心理和培训POR的下一代临床和转化科学家。虽然Palaniappan博士 目前是两项NIH资助的临床试验的主要研究员，她正在寻求支持以追求新颖 心脏代谢健康的机械研究方向，尤其是在2型正常体重的成年人中 糖尿病会影响超过300万美国人，并与更高的心血管死亡率有关。在 此外，该K24提案将利用Palanippan博士的广泛经验来提供创新和 动态设置在POR中训练月经。她的月经可以利用现有的研究平台可用 通过两个大型的随机临床试验（RCT），即强-D（正常重量）和撞击 （超重/肥胖）和现有的机构生物库（斯坦福·吉普尔）。这些生物群样本将 为她未来的研究方向提供基础，该方向将着重于心脏代谢的机械差异 三组的健康：正常的糖尿病患者（强-D），超重/肥胖（影响） 患有糖尿病的个体和正常体重正常血糖个体（斯坦福基因科）。她会使用 人类诱导的多能干细胞，代谢组学和外泌体分析。具体目的如下： AIM 1：表征三组的心脏代谢健康（每组n = 40）。我们假设这一点 糖尿病（NWD）的正常体重患者将是最不健康的心脏代谢，然后超重/OBASE PWD，其次是正常的正常血糖。 AIM 2：研究人类诱导多能干细胞（IPSC）的功能差异，特别是在 三组的心肌细胞和内皮细胞（每组n = 3）。我们假设个人 与正常体重的糖尿病将在心肌细胞（心脏收缩率较小）中表现出更多功能障碍 内皮细胞（一氧化氮输出较少）。 AIM 3：检查三组的代谢物谱（每组n = 40）。我们假设NWD会 与糖尿病的超重或肥胖个体相比，肝糖异构代谢物的代谢产生更多。 AIM 4：评估和比较三组之间的外泌体轮廓（每组n = 40）。我们假设这一点 NWDS将比患有糖尿病的超重/肥胖个体表达更多的抗血管生成miRNA（miR-320） 控制重量。 该建议将确定干预措施的新途径，以预测，预防和治疗死亡率和发病率 正常体重糖尿病。