Nephritogenic Glomerular Epithelial Cell Antigen

说明(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，致力于 免疫介导性红斑狼疮的发病机制及治疗探讨 肾小球损伤。我在印度著名医疗机构接受的培训 美国已经允许我进行几项临床研究，这些研究 现在发表在同行评议的期刊上。我过去两年的研究成果 Years专注于补体非依赖性肾小球的动物模型 伤害，并构成了当前研究提案的背景。这个 波士顿医疗中心的智力刺激工作环境已经开放 给了我一个新的视野，并激励我继续留在我的肾脏病之外 从细胞和分子角度更多地了解肾小球损伤 这是该领域主要权威的最高水平。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 小鼠体内注射阿司匹林后的形态和通透性 用体外培养的肾小管上皮细胞制备抗氨基肽酶A抗体 以下方式： 具体目标1：我们将首先确定在 APA与抗APA共沉淀对培养的GEC的损伤作用 抗体。针对这些假定蛋白的抗体在特定的 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 抗APA亚致死性损伤后的接触和细胞极性。我们会 也研究了抗APA抗体诱导的变化及其可能 APA及其结合蛋白在细胞内分布的相关蛋白 体外和体内。 具体目标3：我们将研究对GEC单层通透性的影响 来自具体目标1和2的适当因素以及其他促进 APA的表达以及APA在细胞内转运的研究 在亚致死伤和康复期间。 总体而言，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所提到的体内观察 上面。这个项目让我可以在三个不同的实验室学习新技能 能够接触到最先进的技术，并将促进我的过渡 成为一名独立的调查员。

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.