Mechanisms for miR-30e Regulated Atherogenic Pathways with Age

miR-30e随年龄调节动脉粥样硬化通路的机制

• 批准号: 8718967
• 负责人: Lina A Shehadeh
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718967
• 关键词: 3' Untranslated Regions; Advisory Committees; Age; Aging; Animal Experiments; Aorta; Arterial Fatty Streak; Atherosclerosis; Back; Basic Science; Binding; Binding Sites; Bioinformatics; Biological Assay; Biology; Blood Vessels; Calcified; Calcium; Cardiac; Cardiology; Cardiovascular system; Cells; Chemicals; Cholesterol; Clinical Research; Collagen; Complex; Computational Biology; Data; Development; Development Plans; Diet; Doctor of Philosophy; Down-Regulation; Elements; Endothelium; Enzymes; Faculty; Fatty acid glycerol esters; Functional disorder; Funding; Genes; Genetic Enhancer Element; Grant; Grant Review; Hares; Hepatic; Hypoxia; Inflammation; Injection of therapeutic agent; Injury; Institutes; Instruction; Journals; K-Series Research Career Programs; LDL Cholesterol Lipoproteins; Laboratories; Lipids; Liver; Luciferases; Measures; Mediating; Medicine; Mentors; Mentorship; Mesenchymal; Mesenchymal Stem Cells; MicroRNAs; Microbiology; Molecular; Molecular Biology; Mus; Mutagenesis; Myofibroblast; NIH 3T3 Cells; Oils; Osteoblasts; Osteogenesis; Pathogenesis; Pathway interactions; Phenotype; Phosphoric Monoester Hydrolases; Plasma; Production; Promoter Regions; Proteins; Regenerative Medicine; Regulation; Research; Research Support; Risk Factors; Rodent; Running; Scientist; Senior Scientist; Silicon Dioxide; Site-Directed Mutagenesis; Smooth Muscle; Smooth Muscle Myocytes; Staining method; Stains; Stem cells; Testing; Therapeutic; Thoracic aorta; Tissues; Training; United States National Institutes of Health; Universities; Vascular Smooth Muscle; Wages; Western Blotting; Writing; age related; angiogenesis; base; bone; calcification; career development; cholesterol biosynthesis; feeding; middle age; new therapeutic target; novel; osteogenic; post-doctoral training; programs; research study; response; responsible research conduct; senescence; stem cell differentiation; symposium; transcription factor

DESCRIPTION (provided by applicant): Dr. Shehadeh has a B.S. in Microbiology, a Ph.D and postdoctoral training in computational biology, and postdoctoral training in cardiovascular research. She is a junior faculty on the tenure track in the Division of Cardiology at the Department of Medicine at UM. This career development award supplements her research background with senior mentorship and lab-based and didactic training in core molecular biology, vascular aging and atherosclerosis. The research plan is based on preliminary observations which support the hypothesis that a microRNA, miR-30e, is down regulated with age and regulates major atherogenic pathways. This hypothesis will be tested along three aims: (1) to assess the effect of miR-30e on cholesterol biosynthesis and bioactivity via Hmgcr regulation, in young, middle-aged, and old atherogenic mice (2) identify the molecular mechanism of miR-30e-mediated regulation of smooth muscle markers, and (3) identify mechanism by which miR-30e suppresses osteogenic differentiation of mesenchymal stem cells (MSCs). Dr. Shehadeh will undertake a career development plan consisting of: 1. Experimental research, laboratory instruction, journal clubs and scientific review and development by her mentors and colleagues. 2. Coursework through the University of Miami graduate program. 3. Intramural seminars and national conferences and symposia. 4. Training in the responsible conduct of research. 5. Guidance by a scientific advisory committee consisting of five senior MDs and one senior Ph.D. 6. Grant writing, grant review, and development of a transition plan aimed at independence. Dr. Shehadeh's molecular and vascular biology mentorship will primarily come from Dr. Keith Webster, director of Vascular Biology Institute (VBI). Dr. Webster is an accomplished NIH-funded vascular biologist who studies mechanisms of hypoxia-regulated angiogenesis, atherosclerosis, aging of mesenchymal stem cells, and therapeutic potential of endothelial progenitor cells. Dr. Shehadeh will be co-mentored by Dr. Joshua Hare, director of the Interdisciplinary Stem Cell Institute (ISCI). Dr. Hare is NIH-funded to investigate basic and clinical research on mesenchymal and cardiac stem cells, has a long track record of research in regenerative medicine, and will provide guidance regarding key mechanistic pathways believed to underlie differentiation of mesenchymal stem cells. This mentorship team will guide Dr. Shehadeh's career development as she executes the research aims of this application in the 3 years, writes her R01 on the 2nd year, and transitions to independence as a research scientist.

描述（由申请人提供）：Shehadeh 博士拥有理学士学位。微生物学博士、计算生物学博士和博士后培训以及心血管研究博士后培训。她是密歇根大学医学系心脏病学系的终身教授。该职业发展奖通过核心分子生物学、血管老化和动脉粥样硬化方面的高级指导以及实验室和教学培训补充了她的研究背景。该研究计划基于初步观察结果，这些观察结果支持以下假设：微小RNA（miR-30e）随着年龄的增长而下调，并调节主要的动脉粥样硬化通路。这一假设将沿着三个目标进行测试：（1）评估 miR-30e 通过 Hmgcr 调节对年轻、中年和老年动脉粥样硬化小鼠中胆固醇生物合成和生物活性的影响（2）确定 miR-30e 介导的平滑肌标志物调节的分子机制，以及（3）确定 miR-30e 抑制动脉粥样硬化斑块成骨分化的机制。 间充质干细胞（MSC）。 Shehadeh 博士将制定职业发展计划，包括： 1. 实验研究、实验室指导、期刊俱乐部以及导师和同事的科学审查和发展。 2. 迈阿密大学研究生课程的课程。 3. 校内研讨会和全国会议和研讨会。 4. 负责任的研究行为培训。 5. 由五名高级医学博士和一名高级博士组成的科学咨询委员会提供指导。 6. 撰写赠款、审查赠款并制定旨在实现独立的过渡计划。 Shehadeh 博士的分子和血管生物学指导将主要来自血管生物学研究所 (VBI) 所长 Keith Webster 博士。 Webster 博士是一位由 NIH 资助的杰出血管生物学家，研究缺氧调节血管生成、动脉粥样硬化、间充质干细胞衰老和内皮祖细胞治疗潜力的机制。 Shehadeh 博士将由跨学科干细胞研究所 (ISCI) 所长 Joshua Hare 博士共同指导。 Hare 博士由 NIH 资助进行调查 间充质和心脏干细胞的基础和临床研究，在再生医学研究方面拥有悠久的记录，并将为间充质干细胞分化的关键机制途径提供指导。这个导师团队将指导 Shehadeh 博士的职业发展，因为她将在 3 年内执行该应用程序的研究目标，并在第二年完成 R01，并过渡为独立的研究科学家。