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.

项目摘要 Anand Rohatgi博士是内科/心脏病学系的副教授 UT西南医疗中心。他建立了一个成功且独立的研究计划 专注于阐明HDL代谢在心血管疾病中的作用。他积极的经历 临床心脏病专家，翻译研究人员和精神将他定位为理想的候选人 K24指导职业发展奖。他对预防性心脏病学和管理的临床关注 动脉粥样硬化疾病为关注HDL的协同翻译研究铺平了道路 代谢和动脉粥样硬化的CV疾病以及对心理学员和教师的热情。 Rohatgi博士有 将流行病学和翻译成这一目标应用于该目标，导致了许多已发布的 关于洞察力的病理生理学和完善的观察结果 与HDL相关的标记，用于风险预测和作为治疗的靶标。这项工作得到了继续的支持 来自NIH/NHLBI（K08> r01），AHA和行业的资金。他还发展了重要的 对临床心血管研究和职业发展的心理学员的专业兴趣。这 K24 Award将通过允许Rohatgi博士的科学职业活动来支持他的专业 通过课程/培训和执行新型项目的开发，这些项目将增强其主要目标 R01并支持未来的独立资金。除了支持科学职业活动外，K24 奖项将直接允许Rohatgi博士购买Mentalship/Leaderslion培训，并增强其更多的能力 深入参与追求K和R01奖项的特定月经，并更广泛地与所有月经互动 在心血管训练中。该提议的总体科学目的是：1）确定 胆固醇外排变异性的遗传因素； 2）确定循环的代谢物和链接的蛋白质 胆固醇外排的变化； 3）确定低胆固醇与高胆固醇的HDL的miRNA货物 外排； 4）评估＃3中鉴定出的不同miRNA对胆固醇外排转运蛋白和外排的影响； 5） 在HDL-C中具有极高升高的人中，确定已知的遗传突变的存在 与升高的HDL-C（SR-B1，CETP，LIPG）和LP（A）水平相关； 6）确定蛋白质组学和脂质组学 HDL分数的签名和功能性在HDL-C中的极高升高的签名和功能。 基因突变和LP升高（a）水平； 7）确定HDL函数测量之间的关系 （胆固醇外排，HDL颗粒数，apo-AI）和高危冠状动脉斑块通过冠状动脉CT评估 在低风险队列中进行成像。