Mentoring Patient-Oriented Research in Deep Lipid Phenotyping for Cardiovascular Disease

指导以患者为导向的心血管疾病深层脂质表型研究

• 批准号: 9903436
• 负责人: Anand Kumar Rohatgi
• 金额: $ 11.59万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903436
• 关键词: ATP binding cassette transporter 1; Angiography; Antiatherogenic; Apolipoprotein A-I; Architecture; Atherosclerosis; Award; Biological; Blood Circulation; CETP gene; Calcium; Cardiac health; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cholesterol; Clinical; Coronary; Coronary heart disease; DNA Sequence Alteration; Deposition; Development; Disease; Disease Pathway; Epidemiology; Event; Excision; Faculty; Functional disorder; Funding; Future; Genetic; High Density Lipoproteins; Human; Impairment; Individual; Industry; Internal Medicine; K-Series Research Career Programs; LIPG gene; Leadership; Link; Lipids; Lipoprotein (a); Measures; Medical center; Mentors; Mentorship; Metabolism; MicroRNAs; Mid-Career Clinical Scientist Award (K24); Modeling; Molecular; Mutation; National Heart, Lung, and Blood Institute; Pathway interactions; Patients; Phenotype; Population Heterogeneity; Positioning Attribute; Preventive; Primates; Process; Proteomics; Psoriasis; Publishing; Reporting; Research; Research Personnel; Risk; Risk Marker; Role; Specificity; Students; Thinness; Time; Training; United States National Institutes of Health; Variant; Work; X-Ray Computed Tomography; atheroprotective; atherosclerosis risk; cardiovascular disorder risk; career; career development; cholesterol transporters; cohort; coronary plaque; density; experience; heart disease risk; high risk; human subject; improved; insight; interest; lifestyle factors; link protein; lipid metabolism; mid-career faculty; mortality; novel; novel strategies; particle; patient oriented research; pre-clinical; prevent; programs; prospective; recruit; research and development; reverse cholesterol transport; targeted treatment; therapeutic target; trait; translational research program; translational scientist

Project Summary Dr. Anand Rohatgi is an Associate Professor in the Department of Internal Medicine/Division of Cardiology at UT Southwestern Medical Center. He has established a successful and independent research program focused on elucidating the role of HDL metabolism in cardiovascular disease. His experiences as an active clinical cardiologist, translational researcher, and mentor have positioned him to be an ideal candidate for the K24 Mentoring Career Development Award. His clinical focus on preventive cardiology and the management of atherosclerotic disease have paved the way for a synergistic translational research program focused on HDL metabolism and atherosclerotic CV disease and a passion for mentoring trainees and faculty. Dr. Rohatgi has applied both epidemiologic and translational POR to this objective, resulting in a number of published observations that have moved the field forward with respect to insights into pathophysiology and refinement of HDL-related markers for risk prediction and as targets of therapy. This work has been supported by continuous funding from the NIH/NHLBI (K08>R01), the AHA, and industry. He has also developed a significant professional interest in mentoring trainees in clinical cardiovascular research and career development. The K24 award will support Dr. Rohatgi’s scientific career activities by allowing him to engage in professional development via coursework/training and execution of novel projects that will enhance the primary aims of his R01 and support future independent funding. In addition to supporting scientific career activities, the K24 award will directly allow Dr. Rohatgi to pursue mentorship/leadership training and enhance his ability to more deeply engage with specific mentees pursuing K and R01 awards and more broadly engage with all mentees in cardiovascular training. The overall scientific aims of this proposal are to: 1) Determine the contribution of genetic factors to variability in cholesterol efflux; 2) Identify circulating metabolites and proteins linked to variation in cholesterol efflux; 3) Determine the miRNA cargo of HDL in those with low versus high cholesterol efflux; 4) Assess the effect of distinct miRNAs identified in #3 on cholesterol efflux transporters and efflux; 5) Among those with extreme elevation in HDL-C, determine the presence of genetic mutations known to correlate with elevated HDL-C (SR-B1, CETP, LIPG) and Lp(a) levels; 6) Determine proteomic and lipidomic signature and functionality of HDL fractions in those with extreme elevations in HDL-C stratified by presence of genetic mutations and elevated Lp(a) levels; 7) Determine the relationship between HDL function measures (cholesterol efflux, HDL particle number, Apo-AI) and high-risk coronary plaque assessed by coronary CT imaging in low risk cohorts.

项目概要 Anand Rohatgi 博士是内科/心脏病科的副教授 他建立了一个成功的独立研究项目。 他的研究重点是阐明高密度脂蛋白代谢在心血管疾病中的作用。 临床心脏病学家、转化研究员和导师使他成为该领域的理想人选 K24 指导职业发展奖他的临床重点是预防心脏病学和管理。 动脉粥样硬化疾病的研究为专注于 HDL 的协同转化研究计划铺平了道路 Rohatgi 博士致力于新陈代谢和动脉粥样硬化性心血管疾病以及指导学员和教师的热情。 将流行病学和转化 POR 应用于这一目标，产生了许多已发表的 这些观察推动了该领域在病理生理学的见解和完善方面的发展 用于风险预测和作为治疗目标的 HDL 相关标记物已得到持续支持。 他还获得了 NIH/NHLBI (K08>R01)、AHA 和行业的资助。 对指导学员进行临床心血管研究和职业发展的专业兴趣。 K24 奖将支持 Rohatgi 博士的科学职业活动，让他能够从事专业研究 通过课程作业/培训和执行新项目进行开发，这将增强他的主要目标 R01 和支持未来的独立资助 除了支持科学职业活动外，K24 该奖项将直接让 Rohatgi 博士能够接受指导/领导力培训，并增强他的更多能力 与追求 K 和 R01 奖项的特定学员进行深入接触，并与所有学员进行更广泛的接触 该提案的总体科学目标是： 1）确定 胆固醇流出变异性的遗传因素；2) 识别与胆固醇流出相关的循环代谢物和蛋白质 3) 确定低胆固醇和高胆固醇人群中 HDL 的 miRNA 含量 流出；4) 评估 #3 中确定的不同 miRNA 对胆固醇流出转运蛋白和流出的影响； 在 HDL-C 极度升高的人群中，确定是否存在已知的基因突变 与 HDL-C（SR-B1、CETP、LIPG）和 Lp(a) 水平升高相关；6) 确定蛋白质组和脂质组 HDL-C 极端升高者中 HDL 分数的特征和功能按存在分层 基因突变和 Lp(a) 水平升高；7) 确定 HDL 功能测量之间的关系 （胆固醇流出、HDL 颗粒数、Apo-AI）和通过冠状动脉 CT 评估的高风险冠状动脉斑块 低风险人群的影像学检查。