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: 10521285
• 负责人: Latha P Palaniappan
• 金额: $ 11.71万
• 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/10521285
• 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; Education; Educational process of instructing; Endothelial Cells; Enrollment; Environment; Etiology; Exhibits; Faculty; Functional disorder; Funding; Gene Pool; Goals; Health; Health Services; Human; Individual; 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; Regimen; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Research Training; Sampling; Science; Technology; Time; Training; Translating; United States; United States National Institutes of Health; Universities; Weight; Weight maintenance regimen; Work; antiangiogenesis therapy; 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; randomized, clinical trials; 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.

项目概要 Latha Palaniappan 博士，医学博士、理学硕士是一位公认的临床研究员，拥有长期的资助记录， 作为新任命的一名新任命的专家，他们在以患者为导向的心脏代谢疾病研究（POR）方面提供专业知识和指导。 斯坦福大学医学教授，丰富的临床研究和教学经验将有助于 Palaniappan 博士是她的导师并培养下一代 POR 临床和转化科学家。 目前是两项 NIH 资助的临床试验的首席研究员，她正在寻求支持以追求新颖 心脏代谢健康的机制研究方向，特别是体重正常的 2 型成人 糖尿病影响着超过 300 万美国人，并与较高的心血管死亡率相关。 此外，这项 K24 提案将利用 Palaniappan 博士丰富的经验来提供创新和 她的学员可以利用现有的研究平台来培训 POR 的动态环境。 通过两项大型随机临床试验 (RCT)，即 STRONG-D（正常体重）和 IMPACT （超重/肥胖），以及现有的机构生物库（斯坦福基因池）这些生物库样本将。 为她未来的研究方向提供基础，该方向将重点关注心脏代谢的机制差异 三组健康状况：正常体重糖尿病患者 (STRONG-D)、超重/肥胖 (IMPACT) 她将使用患有糖尿病的个体和正常体重的血糖正常的个体（Stanford GenePool）。 人类诱导多能干细胞、代谢组学和外泌体分析的具体目标如下： 目标 1：描述三组的心脏代谢健康状况（每组 n=40）。 体重正常的糖尿病患者 (NWD) 心脏代谢最不健康，其次是超重/肥胖 PWD，其次是正常体重正常血糖。 目标 2：研究人类诱导多能干细胞 (iPSC) 的功能差异，特别是 三组的心肌细胞和内皮细胞（每组 n=3）。 体重正常的糖尿病患者会表现出更多的心肌细胞功能障碍（心肌收缩力减弱） 内皮细胞（一氧化氮输出较少）。 目标 3：检查三组的代谢谱（每组 n=40）。我们发现 NWD 会。 比超重或肥胖的糖尿病患者有更多的肝脏糖异生代谢物。 目标 4：评估并比较三组的外泌体概况（每组 n=40）。 NWD 会比超重/肥胖的糖尿病患者表达更多的抗血管生成 miRNA (miR-320) 控制体重。 该提案将确定新的干预途径，以预测、预防和治疗死亡率和发病率 体重正常的糖尿病。