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

项目摘要 博士Anand Rohatgi是内科/心脏科的副教授， UT西南医学中心他建立了一个成功的独立研究项目 致力于阐明HDL代谢在心血管疾病中的作用。他作为特工的经历 临床心脏病学家，翻译研究员和导师使他成为一个理想的候选人， K24导师职业发展奖。他的临床重点是预防心脏病学和管理 动脉粥样硬化性疾病的进展为一个以HDL为重点的协同转化研究项目铺平了道路 代谢和动脉粥样硬化CV疾病和指导学员和教师的热情。Rohatgi博士 应用流行病学和翻译POR这一目标，导致一些出版的 这些观察结果推动了该领域在病理生理学和改善 HDL相关标志物用于风险预测和作为治疗靶点。这项工作得到了持续的支持。 由NIH/NHLBI（K 08> R 01）、AHA和行业资助。他还开发了一个重要的 对指导学员进行临床心血管研究和职业发展的专业兴趣。的 K24奖将支持Rohatgi博士的科学事业活动，使他能够从事专业工作， 通过课程/培训和新项目的执行，将提高他的主要目标的发展 R 01并支持未来的独立供资。除了支持科学事业活动外，K24 该奖项将直接使Rohatgi博士能够进行导师/领导力培训，并提高他的能力， 与特定的学员深入接触，争取获得K和R 01奖项，并更广泛地与所有学员接触 心血管训练本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， 胆固醇流出的变化; 3）确定低胆固醇与高胆固醇患者中HDL的miRNA货物 4）评估#3中鉴定的不同miRNA对胆固醇流出转运蛋白和流出的影响; 5） 在HDL-C极端升高的患者中，确定已知的基因突变的存在， 与HDL-C（SR-B1，CETP，LIPG）和Lp（a）水平升高相关; 6）测定蛋白质组学和脂质组学 HDL-C极度升高患者中HDL组分的特征和功能， 基因突变和Lp（a）水平升高; 7）确定HDL功能指标之间的关系 （胆固醇流出、HDL颗粒数、Apo-AI）和通过冠状动脉CT评估的高危冠状动脉斑块 在低风险队列中进行成像。

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.