The TWIK 2 POTASSIUM CHANNELS ROLE IN THE DEVELOPMENT OF PULMONARY HYPERTENSION

TWIK 2 钾通道在肺动脉高压发展中的作用

基本信息

批准号：
9258380
负责人：
LAVANNYA M. PANDIT
金额：
--
依托单位：
MICHAEL E DEBAKEY VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9258380
关键词：
Affect Age Anesthesiology Blood Pressure Blood Vessels Calcium Calcium Channel Caliber Cardiovascular Physiology Caring Cells Characteristics Clinical Clinical Medicine Critical Care Data Development Disease Disease model Funding Genes Goals Grant Heart Heart Diseases Heart failure Hospitals Human Institution Investigation Knock-out Knockout Mice Knowledge Lead Lung Lung Transplantation Lung diseases Maintenance Measures Medical center Medicine Membrane Potentials Mentors Mentorship Messenger RNA Methodist Church Movement Mus Muscle Cells Pathogenicity Pathologic Pathway interactions Patients Phosphotransferases Physiology Population Potassium Potassium Channel Principal Investigator Property Publications Pulmonary Hypertension Pulmonary Vascular Resistance Pulmonary artery structure Pulmonary vessels Regulation Relaxation Research Research Personnel Research Training Right ventricular structure Role Scientist Secure Side Sleep Smooth Muscle Myocytes Specialist Stress Structure Structure of parenchyma of lung System Testing Therapeutic Tissues Training Training Programs Translational Research United States National Institutes of Health Vascular Smooth Muscle Vasomotor Veterans Wild Type Mouse Work Workload arteriole blood pressure regulation blood pump career career development cerebrovascular college design electrical property experience improved kinase inhibitor loss of function mid-career faculty mouse model novel professor public health relevance skills translational scientist vasoconstriction voltage

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT This career development proposal is designed to provide the Principal Investigator, Dr. Lavannya M. Pandit, with the necessary knowledge, skills, and experience required for her transition to an independent translational researcher in the field of pulmonary hypertension. Dr. Pandit is a well-trained pulmonary specialist who has cared for veterans with pulmonary hypertension due to advanced lung disease for the last eight years. She brings a strong research background to this project including unique skills in obtaining and handling human lung tissue. Dr. Pandit outlines a four-year plan to investigate the basic mechanism by which a novel potassium channel, TWIK-2, regulates pulmonary arterial tone, and specifically how it participates in pulmonary vasoconstriction, a defining characteristic of pulmonary hypertension. This work will be performed under the mentorship of Dr. Rolando Rumbaut, Associate Professor of Medicine, and Section Chief of the Pulmonary/Critical Care/Sleep Medicine section at the Michael E. DeBakey VA Medical Center (MEDVAMC). The co-mentor on this proposal is Dr. Robert M. Bryan, Professor of Anesthesiology and Director of Cerebrovascular Research at Baylor College of Medicine, the affiliated academic institution of the DeBakey VAMC. Both mentors have collaborated with each other as vascular physiologists and have the funding and track record of mentoring young investigators for successful careers in academic medicine. Dr. Pandit also has the support of a team of exceptional collaborators at MEDVAMC, Baylor College of Medicine, and the Methodist Hospital. In addition, Dr. Pandit will acquire training through didactic coursework in cardiovascular physiology within the structure of the Baylor College of Medicine Clinical Scientist Training Program. Dr. Pandit's past academic experiences underscore her commitment to academic medicine and her desire to pursue translational research in pulmonary hypertension. Having completed an NIH research training grant, since 2011, her research has evolved to focus on the role of potassium channels in the regulation of pulmonary vascular tone in an effort to meld her research with her clinical expertise in pulmonary hypertension. She now requires training in pulmonary physiology in both human and murine models of disease during this mentored period of scientific investigation. The research in this proposal will focus on the role of TWIK-2 in the development of pulmonary hypertension. The scientific approach will involve the utilization of pulmonary vessels of mice in which the TWIK-2 gene has been genetically knocked out as well as freshly explanted native human pulmonary vessels from patients with and without pulmonary hypertension, obtained at lung transplantation. Specific Aims of the project are to delineate how TWIK-2 affects the electrical properties of pulmonary smooth muscle cells, intracellular calcium levels, and the contractile properties of pulmonary vessels. The scientific training obtained through this grant will lead to publications and experience that will enable the candidate to secure independent funding within the next four years and establish herself an a translational investigator in pulmonary hypertension.

描述（由申请人提供）：项目摘要/摘要该职业发展建议旨在为首席研究员Lavannya M. Pandit博士提供过渡到肺动脉高压领域的独立翻译研究人员所需的必要知识，技能和经验。 Pandit博士是一位受过良好训练的肺部专家，在过去的八年中，由于晚期肺部疾病而曾照顾患有肺动脉高压的退伍军人。她为该项目带来了强大的研究背景，包括获得和处理人类肺组织的独特技能。潘迪特博士概述了一个四年计划，该计划研究了新型钾通道TWIK-2调节肺动脉张力，特别是它如何参与肺血管收缩，这是肺动脉高压的定义特征。这项工作将在Michael E. Debakey VA医疗中心（MEDVAMC）的肺部/重症监护/睡眠医学部门Rolando Rumbaut博士的指导下进行。该提案的联合学是麻醉学教授兼贝勒医学院脑血管研究主任Robert M. Bryan博士，Debakey VAMC的附属学院。两位导师都以血管生理学家的身份相互合作，并拥有指导年轻研究人员在学术医学领域成功职业的资金和记录。潘迪特博士还得到了MEDVAMC，贝勒医学院和卫理公会医院的杰出合作者团队的支持。此外，潘迪特博士将通过贝勒医学院临床科学家培训计划的结构内的心血管生理学教学课程获得培训。潘迪特（Pandit）博士过去的学术经验强调了她对学术医学的承诺以及她从事肺动脉高压研究的渴望。自2011年以来，她完成了NIH研究培训补助金，她的研究已经发展为重点介绍钾渠道在调节肺血管调节中的作用，以便将她的研究与临床专业知识融合在一起在肺动脉高压中。现在，在这一受过的科学研究期间，她需要在人类和鼠类疾病模型中接受肺部生理学的培训。该提案中的研究将重点介绍TWIK-2在肺动脉高压发展中的作用。科学方法将涉及将TWIK-2基因被遗传击落的小鼠的肺血管，以及在肺移植时获得和没有肺动脉高压的患者的新鲜外植物的天然肺血管。该项目的具体目的是描述TWIK-2如何影响肺平滑肌细胞的电特性，细胞内钙水平以及肺部血管的收缩特性。通过这笔赠款获得的科学培训将导致出版物和经验，这将使候选人能够在未来四年内获得独立资金，并确立自己的肺动脉高压转化调查员。