Role of the Novel MicroRNA-125b in Pulmonary Hypertension Associated with Pulmonary Fibrosis

项目摘要/摘要 奥马尔博士是一名拥有心血管医学博士学位的麻醉师，他正在寻求成为一名 美国国立卫生研究院资助的独立内科医生兼科学家研究#年肺动脉高压的发展 先前存在的肺纤维化(PF)。这项提议的直接目标是巩固他的核心知识 并更新他的实验室和分析技术，同时建立他的出版记录 以及为R01应用建立初步数据。奥马尔博士提出的研究计划旨在 随着一种新的microRNA的发现，了解既存PF中PH的发生机制 这可能是过渡的中介，更长期的目标是了解这一发现是如何实现的 转化为患者的一种新疗法。 奥马尔医生的导师，麻省理工学院麻醉和围手术期医学系的曼苏雷·埃巴利医生 加州大学洛杉矶分校将负责他的科学发展，教他分子和体内和体外 自他完成博士后培训以来开发的靶向技术。他的合作导师， 加州大学洛杉矶分校麻醉学和围手术期医学系的王宜斌医生将帮助他 作为一名内科科学家，要克服与建立独立性相关的许多陷阱。在这一努力中，Dr。 奥马尔将得到一个导师委员会的大力帮助，其中包括夏阳博士，他们将帮助确保他学习 最先进的生物信息学梳理出从PF向PF-PH过渡所涉及的关键新网络 表型。除了积极参与尖端研究，王博士还将补充奥马尔博士的 通过在加州大学洛杉矶分校精心挑选的课程，专注于获得分子 生物学和生物信息学工具、统计熟练程度、拨款撰写和研究的道德行为。 奥马尔博士的项目提案试图剖析几个新的和创新的想法，以推进我们目前的 对既往存在的PF中PH的病理生物学的理解。他开发了一种新的组合动物模型 与PH相关的PF，这是对人类PF-PH的研究结果的概括。一种新的microRNA miR-的鉴定 125b在PF-PH联合用药大鼠肺组织中显著上调，并呈特异性增加。 在SNAI2中，内皮细胞向间充质细胞转化的调节因子是他的建议中的关键发现。是否有可能 靶向miR-125b和SNAI2作为新疗法和生物信息学应用的可能靶点 确定从PF向PF-PH过渡的关键网络的方法代表创新的Pre-Pre 临床策略。

Project Summary/Abstract Dr. Umar is an anesthesiologist with a Ph.D in cardiovascular medicine who is seeking to become a fully independent, NIH funded physician-scientist investigating the development of pulmonary hypertension (PH) in pre-existing pulmonary fibrosis (PF). The immediate goals of this proposal are to solidify his core knowledge in cardiovascular medicine and update his laboratory and analytic techniques while building his publication record and establishing preliminary data for an R01 application. Dr. Umar's proposed research program seeks to understand the mechanisms of development of PH in pre-existing PF with the discovery of a novel microRNA that likely mediates the transition, with the longer term goal of understanding how this discovery can be translated into a novel therapy for patients. Dr. Umar's mentor, Dr. Mansoureh Eghbali in the Department of Anesthesiology and Perioperative Medicine at UCLA, will be responsible for his scientific development, teaching him the molecular and in vivo and in vitro targeting techniques that have been developed since completion of his postdoctoral training. His co-mentor, Dr. Yibin Wang in the Department of Anesthesiology and Perioperative Medicine at UCLA will help him navigate the many pitfalls associated with establishing independence as a physician scientist. In this effort Dr. Umar will be greatly aided by a committee of mentors, including Dr. Xia Yang, who will help ensure he learns state of the art bioinformatics to tease out the key novel networks involved in transition from PF to PF-PH phenotype. Beyond his active participation in cutting-edge research, Dr. Wang will supplement Dr. Umar's knowledge base through carefully selected coursework at UCLA, focusing on the acquisition of molecular biology and bioinformatics tools, statistical proficiency, grant writing and the ethical conduct of research. Dr. Umar's project proposal seeks to dissect the several new and innovative ideas for advancing our current understanding of the pathobiology of PH in pre-existing PF. He has developed a novel combined animal model of PF associated with PH, that recapitulates findings of human PF-PH. Identification of a novel microRNA, miR- 125b, which is significantly upregulated in the lungs of rats with combined PF-PH, along with specific increase in Snai2, a regulator of endothelial to mesenchymal transition, are key finding in his proposal. The possibility of targeting miR-125b and Snai2 as possible targets for novel therapeutics and the use of bioinformatics approach to identify the key networks mediating the transition from PF to PF-PH represent innovative pre- clinical strategies.