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: 10397015
• 负责人: Anand Kumar Rohatgi
• 金额: $ 11.48万
• 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/10397015
• 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; lipidomics; mid-career faculty; mortality; novel; novel strategies; particle; patient oriented research; pre-clinical; prevent; programs; prospective; recruit; research and development; reverse cholesterol transport; risk prediction; 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.

项目总结