Mechanisms for miR-30e Regulated Atherogenic Pathways with Age

描述（由申请人提供）：Shehadeh博士拥有学士学位在微生物学，博士和计算生物学博士后培训，并在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终身教职的初级教师。这个职业发展奖补充了她的研究背景与高级导师和实验室为基础的核心分子生物学，血管老化和动脉粥样硬化的教学培训。该研究计划基于初步观察，这些观察支持以下假设：microRNA，miR-30 e，随着年龄的增长而下调，并调节主要的动脉粥样硬化途径。该假设将沿着沿着三个目的进行检验：（1）评估miR-30 e通过Hmgcr调节对年轻、中年和老年致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）鉴定miR-30 e介导的平滑肌标志物调节的分子机制;以及（3）鉴定miR-30 e抑制间充质干细胞（MSC）成骨分化的机制。Shehadeh博士将进行职业发展计划，包括：1。实验研究，实验室教学，期刊俱乐部和科学审查和发展，她的导师和同事。2.通过迈阿密大学研究生课程的课程。3.校内研讨会和全国会议及专题讨论会。4.培训负责任地开展研究。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.赠款写作，赠款审查，并制定一个过渡计划，旨在独立。Shehadeh博士的分子和血管生物学导师将主要来自血管生物学研究所（VBI）主任基思韦伯斯特博士。韦伯斯特博士是一位有成就的NIH资助的血管生物学家，他研究缺氧调节的血管生成、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）主任约书亚黑尔博士共同指导。Hare博士是NIH资助的一项研究 关于间充质干细胞和心脏干细胞的基础和临床研究，在再生医学研究方面有着悠久的历史，并将为据信是间充质干细胞分化基础的关键机制途径提供指导。Shehadeh博士将在3年内执行本申请的研究目标，在第二年撰写R 01，并过渡到独立的研究科学家，该指导团队将指导她的职业发展。

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.