Re-Induction of Developmental Programs during Chronic Renal Injury

首席研究员的长期目标是指导一个基础科学研究计划，探索 肾纤维化的发病机制。为了实现这一目标，他参加了博士后奖学金计划， 在接受了肾成纤维细胞和细胞外基质生物学的研究培训后， 年在哥廷根大学担任肾小管上皮细胞生物学和临床肾脏病助教 德国。目前的博士后研究是在拉古·卡鲁里博士的指导下进行的。 他的实验室非常适合在现有的和新的分子技术和转基因方面提供指导。 动物研究，以促进独立职业生涯的开始。这里提出的研究项目主要集中在 探讨有助于保护肾脏免受损伤的内源性再生机制及其在 设计治疗方法以保护肾脏免受慢性进行性肾脏疾病的影响。的中心假说 这一建议是肾损伤的恢复遵循与那些类似的路径，即 调节肾脏发育。这种想法是基于之前的研究，这些研究表明 骨形态发生蛋白-7(BMP-7)，一种参与肾小管形成的生长因子 肾脏发育，促进慢性肾脏疾病的消退。这些先前的研究表明， BMP-7可逆转损伤的肾小管上皮细胞向间充质转化(EMT)， 导致成纤维细胞堆积。此外，BMP-7还可诱导延髓的表型改变 肾成纤维细胞类似于间充质向上皮细胞过渡，再生上皮细胞。这项研究旨在 在这项应用中提出的是围绕着测试成纤维细胞在肾脏修复中的潜在作用 他们试图在分子水平上进一步分析初步的表型观察。

The Principal Investigator's long-term goal is to direct a basic science research program exploring the pathogenesis of kidney fibrosis. To achieve this goal he has entered a post-doctoral fellowship program, which is centered around extracellular matrix biology following his research training in renal fibroblast and tubular epithelial cell biology coupled with a clinical Nephrology clerkship at the University of Goettingen in Germany. The current postdoctoral fellowship research is conducted under supervision of Dr. Raghu Kalluri. His laboratory is well suited to provide guidance in established and new molecular techniques and transgenic animal studies to foster the start of an independent career. The research project proposed here centers on exploring endogenus regenerative mechanisms, which facilitate protection from kidney injury and its use in designing therapies to protect the kidney from chronic progressive kidney disease. The central hypothesis of this proposal is that the recovery from renal injury follows pathways, which are similar to those, which mediate kidney development. Such thinking is based on previous studies, which demonstrate that administration of bone morphogenic protein-7 (BMP-7), a growth factor involved in tubulogenesis during kidney development, facilitates regression of chronic kidney disease. These previous studies suggest that BMP-7 may reverse epithelial to mesenchymal transition (EMT) involving injured tubular epithelial cells, leading to accumulation of fibroblasts. Additionally, BMP-7 also induces phenotypic changes in medullary renal fibroblasts resembling mesenchymal to epithelial transition, regenrating epithelial cells. The study aims proposed in this application are centered around testing the potential role of fibroblasts in the repair of renal injury and they attempt to further analyze the preliminary phenotypic observation at a molecular level.