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

新型 MicroRNA-125b 在与肺纤维化相关的肺动脉高压中的作用

• 批准号: 10162649
• 负责人: Soban Umar
• 金额: $ 17.58万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162649
• 关键词: Address; Affect; Anesthesiology; Animal Model; Automobile Driving; Bioinformatics; Blood Vessels; Cardiovascular system; Cell Proliferation; Data; Development; Disease; Down-Regulation; Educational process of instructing; Endothelium; Ensure; Ethics; Funding; Goals; Grant; Human; In Vitro; Investigation; Knowledge; Laboratories; Learning; Lung; Lung Transplantation; Lung diseases; Mediating; Medicine; Mentors; Mesenchymal; MicroRNAs; Modeling; Molecular; Molecular Biology; Morbidity - disease rate; Patients; Perioperative; Pharmaceutical Preparations; Phenotype; Physicians; Pre-Clinical Model; Prognosis; Publications; Pulmonary Fibrosis; Pulmonary Hypertension; Pulmonary artery structure; Rattus; Research; Role; Scientist; Smooth Muscle Myocytes; Techniques; Therapeutic Uses; Translating; United States National Institutes of Health; Up-Regulation; Update; Vascular Diseases; Vascular remodeling; Writing; Yang; bioinformatics tool; effective therapy; hypertension prevention; in vivo; innovation; insight; knock-down; knowledge base; mortality; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; overexpression; post-doctoral training; pre-clinical; prevent; prognostic significance; programs; pulmonary artery endothelial cell; targeted treatment; transcription factor; transcriptome sequencing

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.

项目总结/摘要 博士奥马尔是一名麻醉师，拥有心血管医学博士学位，他正在寻求成为一名全面的 独立的，NIH资助的医生科学家调查肺动脉高压（PH）的发展， 肺纤维化（PF）。这个建议的直接目标是巩固他的核心知识， 心血管医学和更新他的实验室和分析技术，同时建立他的出版记录 并为R 01应用建立初步数据。奥马尔博士提出的研究计划旨在 通过发现一种新的microRNA，了解预先存在的PF中PH的发展机制 这可能会调解过渡，长期目标是了解这一发现如何 转化为一种新的治疗方法。 博士Umar的导师，Mansoureh Eghbali博士在麻醉学和围手术期医学系， 加州大学洛杉矶分校，将负责他的科学发展，教他的分子和在体内和体外 瞄准自完成博士后培训以来开发的技术。他的共同导师， 博士加州大学洛杉矶分校麻醉和围手术期医学系的王一斌将帮助他 导航与建立独立作为一个医生科学家的许多陷阱。在这一努力博士。 奥马尔将得到包括夏阳博士在内的导师委员会的大力帮助， 最先进的生物信息学梳理出从PF到PF-PH转变所涉及的关键新网络 表型除了积极参与前沿研究，王博士还将补充欧玛博士的工作， 通过加州大学洛杉矶分校精心挑选的课程学习知识基础，重点是分子的获取 生物学和生物信息学工具，统计能力，赠款写作和研究的道德行为。 博士欧麦尔的项目提案旨在剖析几个新的和创新的想法，以推进我们目前的 了解PH的病理生物学在预先存在的PF。他已经开发了一种新的组合动物模型 PF与PH相关的研究，概括了人类PF-PH的发现。 125 b，其在具有组合PF-PH的大鼠的肺中显著上调，沿着特异性增加 Snai 2是内皮细胞向间充质细胞转化调节因子，这是他提出的关键发现。的可能性 靶向miR-125 b和Snai 2作为新疗法的可能靶标和生物信息学的应用 确定调解从PF到PF-PH过渡的关键网络的方法代表了创新的预 临床策略