Sox6 Role in Renin Expression During Juxtaglomerular Cells Expansion

项目摘要 该提案详细介绍了一项为期五年的指导培训计划，旨在促进以下人员的职业发展和晋升 博士何塞a.戈麦斯，变成一个独立的调查员。戈麦斯博士是一个研究导师在司 范德比尔特大学的临床药理学。他毕业于凯斯药理学博士学位 西储大学。2009年，他加入了维克托J. Dzau博士的实验室，担任博士后研究员， 杜克大学，并开始对血压控制和高血压感兴趣。他加入了范德比尔特 2015年在大学医学系/临床药理学系担任研究导师。 在K01获奖期间，他将与Harrison博士、Pozzi博士和Harris博士密切合作。 作为博士后研究员，他定义了肾间充质基质细胞在血压中的作用， 体内平衡他发现成人肾脏干/祖细胞具有分化为JG样细胞的能力， 细胞和/或有助于JG细胞扩增。在第二个项目中，他参与了一项研究，发现肾脏 MSC通过Cox2-PGE2-EP4途径募集。他还研究了成年人 干细胞分化成专门的组织，并确定Sfrp2在心脏中起着重要作用， 通过促进c-Kit+心脏祖细胞向心肌细胞的分化来促进再生。现在作为一个 范德比尔特大学的临床讲师，在大卫哈里森博士的指导下，他正在阐明 在肾祖细胞向肾小球旁细胞的编程中发挥作用的转录调节因子 细胞他发现Sox6在发育中的肾脏和成人肾脏中的产生肾素的细胞中表达 刺激后促进JG细胞扩增。这表明Sox 6在肾素细胞命运中的新作用 说明书，从而在肾脏发育和生理学。他的初步数据显示，Sox 6是 在体外将肾间充质干细胞转化为表达肾素的细胞所需的。在K01提案中，他将 描述了Sox 6在血压稳态和肾小球旁细胞命运中的新的关键功能。的 K01中提出的研究旨在确定Sox 6在血压中发挥作用的机制 内稳态，并将为高血压的治疗开辟新的机会。 在他计划的研究期间，Gomez博士将在体外和体内研究方法方面积累经验。 高血压此外，他的培训计划包括教学课程、研讨会和参加职业培训。 在范德比尔特的发展计划，促进青年教师的保留和任期。博士 哈里森和戈麦斯博士为他的职业发展和培训活动制定了一个时间轴， 使他能够竞争资金，并发展成为高血压领域的独立调查员。 100%的时间将被用于与其职业发展直接相关的活动。Vanderbilt 大学的研究和学术环境对于学员的职业发展来说是非常特殊的。

PROJECT SUMMARY This proposal details a five-year mentored training program for the career development and advancement of Dr. Jose A. Gomez, into an independent investigator. Dr. Gomez is a Research Instructor in the Division of Clinical Pharmacology at Vanderbilt University. He graduated with a Doctorate in Pharmacology from Case Western Reserve University. In 2009, he joined Dr. Victor J. Dzau's laboratory as a Post-Doctoral Fellow at Duke University, and became interested in blood pressure control and hypertension. He joined Vanderbilt University as Research Instructor in the Department of Medicine/Division of Clinical Pharmacology in 2015. During his K01 award, he will work with Dr. Harrison in close collaboration with Dr. Pozzi and Dr. Harris. As a postdoctoral fellow he defined the role of renal mesenchymal stromal cells in blood pressure homeostasis. He found that adult kidney stem/progenitor cells have the capacity to differentiate into JG-like cells and/or contribute to JG cell expansion. In a second project he contributed to a study that found that renal MSCs are recruited via the Cox2-PGE2-EP4 pathway. He aslo investigated the mechanisms by which adult stem cells differentiate into specialized tissues, and determined that Sfrp2 plays an essential role in cardiac regeneration by promoting the differentiation of c-Kit+ cardiac progenitor cells to cardiomyocytes. Now as a Clinical Instructor in Vanderbilt University, under the mentorship of Dr. David Harrison, he is elucidating the transcriptional regulators that play a role in the programming of renal progenitor cells into Juxtaglomerular cells. He found that Sox6 is expressed in renin producing cells in the developing kidney and in the adult kidney after stimulation that promotes JG cell expansion. This suggests a novel role for Sox6 in renin cell fate specification and thereby in renal development and physiology. His preliminary data shows that Sox6 is required in the conversion of renal MSCs to renin expressing cells in vitro. In this K01 proposal, he will characterize a new key function of Sox6 in blood pressure homeostasis and Juxtaglomerular cell fate. The studies proposed in this K01, aim at identifying the mechanisms by which Sox6 plays a role in blood pressure homeostasis, and will open new opportunities for the therapy of hypertension. During his planned research, Dr. Gomez will become experienced in in vitro and in vivo approaches to study hypertension. In addition, his training plan includes didactic courses, seminars, and participation in career development programs at Vanderbilt that promote the retention and tenure of junior faculty members. Dr. Harrison and Dr. Gomez have developed a timeline for his career development and training activities that will enable him to compete for funding and to develop into an independent investigator in the field hypertension. 100% of his time will be protected for activities directly related to his career development. Vanderbilt University's research and academic environment is highly exceptional for trainee career development.