Nephritogenic Glomerular Epithelial Cell Antigen

肾炎性肾小球上皮细胞抗原

• 批准号: 6897530
• 负责人: Sumant Singh Chugh
• 金额: $ 12.59万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897530
• 关键词: aminopeptidase; autoantibody; autoantigens; dexamethasone; enzyme inhibitors; genetically modified animals; immunoprecipitation; kidney disorder; laboratory mouse; membrane permeability; pathologic process; protein biosynthesis; protein localization; protein transport; proteinuria; renal glomerulus; tissue /cell culture

DESCRIPTION (adapted from the application) My goal is to be an outstanding basic scientist and clinician devoted to investigating the pathogenesis and treatment of immunologically mediated glomerular injury. My training from reputed medical institutions in India and the United States has allowed me to conduct several clinical studies that are now published in peer reviewed journals. My research effort over the past two years was focused on an animal model of complement-independent glomerular injury, and has formed the background for the current research proposal. The intellectually stimulating work environment at Boston Medical Center has opened a new horizon for me, and has inspired me to stay on beyond my nephrology fellowship to learn more about glomerular injury at a cellular and molecular level from leading authorities in the field. Under the guidance of my mentors, I plan to study changes in visceral glomerular epithelial cell (visceral GEC) morphology and permeability noted in-vivo in mice following injection of anti-aminopeptidase A (APA) antibodies, using cultured GECs (in-vitro) in the following manner: Specific Aim 1: We will first identify proteins that play a role in APA-mediated injury in cultured GECs by co-precipitating them with anti-APA antibodies. Antibodies to these putative proteins have applications in Specific Aims 2 and 3. Specific Aim 2: We will identify alterations in cell-matrix contact, cell-cell contact and cell polarity following sub-lethal injury with anti-APA. We will also study changes induced by antibodies against APA and its putative associated proteins in the distribution of APA and its associated proteins in vitro and in vivo. Specific Aim 3: We will study the impact on GEC monolayer permeability of appropriate factors from Specific Aims 1 and 2 and others that upregulate the expression of APA, followed by studies on the intracellular transport of APA during sub-lethal injury and recovery. Overall, our characterization of APA-mediated cell injury and its effects on GEC-permeability will help us understand the in-vivo observations mentioned above. This project allows me to learn new skills at three different labs that have access to state-of-the-art technology, and will facilitate my transition towards becoming an independent investigator.

描述（改编自应用程序） 我的目标是成为一名杰出的基础科学家和临床医生， 研究免疫介导的 肾小球损伤我在印度著名的医疗机构接受的培训， 美国允许我进行几项临床研究， 现在发表在同行评审的期刊上。我过去两年的研究成果 多年来一直专注于补体非依赖性肾小球疾病的动物模型， 伤害，并构成了当前研究提案的背景。的 波士顿医疗中心的智力刺激工作环境已经开放 这对我来说是一个新的视野，并激励我继续留在我的肾病学之外。 奖学金，以了解更多关于肾小球损伤的细胞和分子 从该领域的主要当局的水平。在我导师的指导下， 我计划研究内脏肾小球上皮细胞（内脏GEC）的变化 在小鼠体内注射后观察到的形态学和渗透性 抗氨肽酶A（阿帕）抗体，使用培养的GEC（体外）， 如下方式： 具体目标1：我们将首先确定在以下方面发挥作用的蛋白质： APA介导的体外培养GECs损伤（抗APA共沉淀） 抗体的针对这些推定蛋白质的抗体在特异性免疫中具有应用。 目标2和3。 具体目标2：我们将确定细胞-基质接触、细胞-细胞接触和细胞-细胞接触的改变。 接触和细胞极性后亚致死损伤与抗APA。我们将 还研究了抗阿帕抗体及其推定的 阿帕及其相关蛋白的分布 体外和体内。 具体目标3：我们将研究GEC单层渗透性的影响， 来自特定目标1和2的适当因子以及其他上调 阿帕的表达，以及阿帕细胞内转运的研究 在亚致命伤害和恢复过程中。 总之，我们对APA介导的细胞损伤及其对 GEC渗透性将帮助我们理解上述体内观察结果 以上这个项目让我在三个不同的实验室学习新技能， 我能接触到最先进的技术， 成为一名独立调查员