Angiotensin Metabolite Formation by Podocytes: Implications in Glomerular Injury

描述(由申请人提供)： 这是一个新的K08应用程序，其目的是为南卡罗来纳医科大学的候选人胡安·卡洛斯·Q·韦莱斯博士提供培训和指导的研究环境。MUSC是南卡罗来纳州最大的医疗综合体的一部分，拥有140,000平方英尺专门用于研究实验室空间和一个多学科大学研究资源设施(URRF)，其中包含可供研究人员使用的共享资源，包括：高级图像分析、基因靶向和基因敲除鼠标设施、核磁共振设施和已建立的质谱学设施。 候选人。这位候选人是MUSC肾病学部的一名新的全职终身教职助理教授。他是一位崭露头角的年轻临床医生兼科学家，在他职业生涯的早期曾两次获得基础科学研究奖项，最近在一家著名的同行评议期刊上发表了一篇第一作者论文。他拥有非常适合担任KO8赞助商的专业素质。韦莱斯博士概述了一项计划，即发展一个成功的独立资助实验室，并获得必要的经验，以保持与肾脏研究相关的富有成效的科学事业。为了确保这些目标的实现，维莱兹博士组建了一个非常合格的科学家指导委员会，他们在获得外部资金和维护成功的研究实验室方面拥有广泛的记录。 研究提案。该提案旨在包括一系列专注于假设驱动的实验，这些实验将深入了解肾小球内激素调节的机制，以及它们与导致进行性肾脏疾病的途径的关系。具体地说，该提案的重点是检查肾小球内血管紧张素-II和其他血管紧张素代谢物之间的平衡，以及肾小球足细胞在该系统中所起的作用。研究建议的目标是建立一个技术知识和专业知识的基础，通过这些基础可以建立一个长期的研究计划。 公共卫生相关性：本文概述的研究将增加对肾脏内现有机制的理解，以抵消血管紧张素-II激素的作用。2000万美国人患有慢性肾脏疾病，其他许多人也有感染这种疾病的风险。对血管紧张素II的药理阻断是FDA批准的唯一可用的治疗方法。尽管接受了这种治疗，但相当大比例的受影响患者继续进展到疾病的终末期。更好地了解肾脏的机制应该会导致直接靶向的治疗。这些疗法将改善受影响个人的生活质量和寿命。

DESCRIPTION (provided by applicant): This is a new K08 application, the purpose of which is to provide training and a mentored research environment for the candidate, Dr. Juan Carlos Q. Velez, at the Medical University of South Carolina. MUSC is part of South Carolina's largest medical complex with 140,000 ft2 dedicated to research laboratory space and a multidisciplinary University Research Resource Facility (URRF) that contains shared resources available to investigators including: Advanced Image Analysis; Gene targeting and Knockout Mouse Facility; Nuclear Magnetic Resonance Facility, and an established Mass Spectrometry Facility. Candidate. The candidate is a new full-time tenure-track assistant professor in the Division of Nephrology, at the MUSC. He is an up-and-coming young clinician-scientist that has a track record of two awards in basic science research during his early career and one recent first-author publication in a prestigious peer-reviewed journal. He possesses professional qualities highly suited for KO8 sponsorship. Dr. Velez has outlined a plan to develop a successful independently funded laboratory and to gain experience necessary to maintain a productive scientific career relevant to kidney research. To ensure these goals are met, Dr. Velez has assembled a highly qualified mentorship committee of scientists who have extensive track records in obtaining extramural funding and maintaining successful research laboratories. Research Proposal. The proposal has been designed to include a focused hypothesis-driven series of experiments that will yield insight into mechanisms of hormonal regulation within the kidney glomerulus and their relationship with pathways that lead to progressive kidney diseases. Specifically, the proposal is focused on examining the balance between intraglomerular angiotensin-II and other angiotensin metabolites and the role that glomerular podocytes play in that system. The goal of the research proposal is to establish a foundation of technical knowledge and expertise by which a long-term research program can be established. PUBLIC HEALTH RELEVANCE: The studies outlined herein will add to the understanding of the existing mechanisms within the kidney to counterbalance the actions of the hormone angiotensin-II. Twenty million American have chronic kidney disease and many others are on risk of acquiring it. Pharmacological blockade of angiotensin-II constitutes the only FDA-approved therapy available. Despite receiving this therapy, a significant percentage of the affected patients continue to progress to the end-stage form of the disease. Better understanding of the mechanisms of in the kidney should lead to therapies that can directly target. These therapies would improve both quality and length of life of affected individuals.