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

项目总结/摘要 本职业发展计划旨在为校长提供 研究者，Lavannya M.博士潘伟迪，有必要的知识，技能， 她的过渡到一个独立的翻译研究者在 肺动脉高压领域。潘迪特医生是一位训练有素的肺部专家， 一直在照顾因晚期肺病而患肺动脉高压的退伍军人， 过去的八年她为这个项目带来了强大的研究背景，包括 在获取和处理人类肺组织方面的独特技能。潘伟迪博士概述了一项为期四年的 计划研究一种新的钾通道TWIK-2， 调节肺动脉张力，特别是它如何参与肺动脉张力， 血管收缩是肺动脉高压的一个特征。这项工作将 在罗兰多·伦鲍特博士的指导下进行，副教授 医学，肺/重症监护/睡眠医学科科长， 迈克尔·E。DeBakey VA医疗中心（MEDVAMC）。这方面的共同导师 罗伯特·M博士。Bryan，麻醉学教授兼 贝勒医学院的脑血管研究， 关于DeBakey VAMC两个导师都互相合作， 血管生理学家，并有资金和指导年轻人的记录 研究人员在学术医学的成功职业生涯。潘伟迪博士还拥有 支持一个团队的特殊合作者在MEDVAMC，贝勒大学 医学和卫理公会医院此外，潘伟迪博士将获得培训， 通过教学课程在心血管生理学的结构内， 贝勒医学院临床科学家培训计划。 Pandit博士过去的学术经历强调了她对学术的承诺 医学和她追求肺动脉高压转化研究的愿望。 在完成了NIH研究培训补助金后，自2011年以来，她的研究已经发展 关注钾通道在肺血管张力调节中的作用 努力将她的研究与她在肺动脉高压方面的临床专业知识结合起来。 她现在需要在人类和小鼠模型中进行肺生理学的培训， 在这段科学研究的指导时期。 本提案中的研究将集中在TWIK-2在开发中的作用 肺动脉高压科学方法将涉及利用 TWIK-2基因已被基因敲除的小鼠的肺血管 以及来自患有和 无肺动脉高压，在肺移植时获得。具体目标 项目是描绘TWIK-2如何影响肺的电特性， 平滑肌细胞，细胞内钙水平，和收缩特性， 肺血管通过这项赠款获得的科学培训将导致 出版物和经验，使候选人能够确保独立 在接下来的四年内获得资金，并成为一名翻译研究员， 肺动脉高压

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.