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

项目摘要/摘要 这份职业发展提案旨在为校长提供 调查员Lavannya M.Pandit博士，具有必要的知识、技能和 她过渡到独立翻译研究员所需的经验 肺动脉高压领域。潘伟迪医生是一位训练有素的肺部专家 曾照顾因晚期肺部疾病而患有肺动脉高压的退伍军人 过去的八年里。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个为期四年的 计划研究一种新的钾通道Twik-2， 调节肺动脉张力，特别是它是如何参与肺循环的。 血管收缩，这是肺动脉高压的一个明显特征。这项工作将是 在罗兰多·伦博博士的指导下演出，罗兰多·伦博博士是 和肺/重症监护/睡眠医学科科长，地址： Michael E.DeBakey退伍军人医疗中心(MEDVAMC)。这件事上的共同导师 建议是麻醉学教授、麻省理工学院院长罗伯特·M·布莱恩博士 贝勒医学院附属学术机构脑血管研究 DeBakey VAMC机构。这两位导师都曾作为 血管生理学家，并有资金和跟踪记录指导年轻人 在学术医学领域取得成功的研究人员。潘伟迪博士也有 贝勒学院MEDVAMC杰出合作者团队的支持 医学和卫理公会医院。此外，潘伟迪博士还将接受培训 通过教学课程讲授心血管生理学的结构 贝勒医学院临床科学家培训计划。 潘伟迪博士过去的学术经历突显了她对学术的承诺 医学和她在肺动脉高压方面进行转化研究的愿望。 自2011年以来，在完成了NIH的研究培训拨款后，她的研究取得了进展 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培训 疾病在这一科学研究的指导期内。 这项提案中的研究将集中在twik-2在发育中的作用。 肺动脉高压的症状。科学方法将涉及到利用 Twik-2基因被基因敲除的小鼠肺血管 以及新鲜移植的人肺血管，来自和 无肺动脉高压，在肺移植时获得。《公约》的具体目标 项目是描绘Twik-2如何影响肺组织的电特性 平滑肌细胞、细胞内钙水平和血管收缩特性 肺血管。通过这笔赠款获得的科学培训将导致 使候选人能够确保独立的出版物和经验 在未来四年内提供资金，并成为一名翻译调查员 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.