Sox6 Role in Renin Expression During Juxtaglomerular Cells Expansion

Sox6 在肾小球旁细胞扩增过程中肾素表达中的作用

基本信息

批准号：
10393935
负责人：
Jose A. Gomez
金额：
$ 4.43万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2023-01-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10393935
关键词：
Adult Affect American Angiotensin I Angiotensinogen Angiotensins Binding Blood Pressure Cardiac Cardiac Myocytes Cardiovascular Diseases Career Mobility Cell Differentiation process Cells Clinical Clinical Pharmacology Collaborations Cyclic AMP Data Development Dinoprostone Disease Down-Regulation Environment Faculty Funding Genetic Transcription Heart failure Homeostasis Human Hypertension In Vitro Juxtaglomerular Cell Kidney Knock-out Laboratories Lead Medicine Mentored Research Scientist Development Award Mentors Mentorship Mesenchymal Differentiation Microarray Analysis Molecular Mus Myocardial Infarction Organ Pathway interactions Patients Peripheral Vascular Diseases Pharmacology Physiology Play Population Postdoctoral Fellow Process Program Development Proto-Oncogene Protein c-kit Recovery Renin Research Research Personnel Role SOX6 gene Scheme Single Nucleotide Polymorphism Smooth Muscle Myocytes Sodium Stress System Testing Time TimeLine Tissues Training Training Activity Training Programs Transgenic Mice United States Universities WFDC2 gene Work adult stem cell arteriole blood pressure regulation cardiac regeneration career development cell fate specification experience in vivo instructor interest knock-down member mesenchymal stromal cell novel novel therapeutics promoter recruit response stem stem cell differentiation stem cells stroke risk

项目摘要

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.

项目摘要该建议详细介绍了一项为期五年的指导培训计划，以实现职业发展和进步何塞·戈麦斯（Jose A. Gomez）博士，成为一名独立研究员。戈麦斯博士是部门的研究讲师范德比尔特大学的临床药理学。他毕业于CASE的药理学博士学位西部储备大学。 2009年，他加入Victor J. Dzau博士的实验室，担任博士后研究员杜克大学，对血压控制和高血压感兴趣。他加入了范德比尔特大学于2015年担任医学系/临床药理学系研究教练。在他的K01奖中，他将与哈里森博士与Pozzi博士和Harris博士密切合作。作为博士后研究员，他定义了肾脏间充质细胞在血压中的作用稳态。他发现成年肾脏茎/祖细胞具有分化为JG样的能力细胞和/或有助于JG细胞扩张。在第二个项目中，他为一项研究发现肾脏做出了贡献 MSC通过COX2-PGE2-EP4途径招募。他ASLO调查了成人的机制干细胞分化为专用组织，并确定SFRP2在心脏中起着至关重要的作用通过促进C-KIT+心脏祖细胞对心肌细胞的分化来再生。现在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，他正在阐明转录调节器在肾脏祖细胞编程中发挥作用细胞。他发现Sox6在发育中的肾脏和成年肾脏中的肾素产生细胞中表达刺激促进JG细胞扩张。这表明Sox6在肾素细胞命运中的新作用规格，从而在肾脏发展和生理学中。他的初步数据表明Sox6是在肾脏MSC转化为肾素表达细胞的体外所必需的。在这个K01提案中，他将表征Sox6在血压稳态和近后细胞命运中的新关键功能。这在本K01中提出的研究旨在识别SOX6在血压中起作用的机制体内平衡，并将为治疗高血压提供新的机会。在计划的研究中，戈麦斯博士将在体外和体内研究中经验丰富高血压。此外，他的培训计划还包括教学课程，研讨会和参与职业范德比尔特（Vanderbilt）的发展计划促进了初级教师的保留和任期。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表使他能够竞争资金并发展成为现场高血压的独立调查员。他的时间的100％将受到与他的职业发展直接相关的活动的保护。范德比尔特大学的研究和学术环境对于受训人员的职业发展非常出色。