Mechanisms for miR-30e Regulated Atherogenic Pathways with Age

简介（申请人提供）：Shehadeh博士拥有微生物学学士学位，计算生物学博士和博士后学位，心血管研究博士后学位。她是澳大医学院心脏病科终身教职的初级教员。这个职业发展奖项补充了她在核心分子生物学、血管老化和动脉粥样硬化方面的高级指导和实验室教学培训的研究背景。该研究计划基于初步观察结果，初步观察结果支持以下假设，即microRNA miR-30e随着年龄的增长而下调，并调节主要的动脉粥样硬化途径。这一假设将沿着三个目标进行测试：(1)评估miR-30e通过Hmgcr调节对胆固醇生物合成和生物活性的影响，在年轻，中年和老年动脉粥样硬化小鼠中；(2)确定miR-30e介导的平滑肌标志物调节的分子机制；(3)确定miR-30e抑制间充质干细胞（MSCs）成骨分化的机制。Shehadeh博士将进行一项职业发展计划，包括：由她的导师和同事进行实验研究，实验室指导，期刊俱乐部和科学评论和发展。2. 迈阿密大学研究生课程。3. 校内讨论会、全国会议和专题讨论会。4. 培训负责任的研究行为。5. 5 .由5名高级博士和1名高级博士组成的科学顾问委员会指导。奖助金的写作、奖助金的审查，以及以独立为目标的过渡计划的发展。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）主任Keith Webster博士。韦伯斯特博士是美国国立卫生研究院资助的血管生物学家，研究缺氧调节血管生成、动脉粥样硬化、间充质干细胞衰老机制和内皮祖细胞的治疗潜力。Shehadeh博士将由跨学科干细胞研究所（ISCI）主任Joshua Hare博士共同指导。黑尔博士由美国国立卫生研究院资助进行调查

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.