Re-Induction of Developmental Programs during Chronic Renal Injury

首席研究员的长期目标是指导一项基础科学研究计划， 肾纤维化的发病机制。为了实现这一目标，他进入了博士后奖学金计划， 这是围绕细胞外基质生物学继他的研究训练，在肾成纤维细胞， 年在哥廷根大学的肾小管上皮细胞生物学和临床肾病学实习 德国。目前的博士后奖学金研究是在Raghu Kaghui博士的监督下进行的。 他的实验室非常适合为建立和新的分子技术和转基因技术提供指导。 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集中在 探索有助于保护免受肾损伤的内源性再生机制，以及其在 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。的中心假设 该提议是，肾损伤的恢复遵循与以下途径相似的途径： 介导肾脏发育。这种想法是基于以前的研究，这些研究表明， 骨形态发生蛋白-7（BMP-7），一种在骨形成过程中参与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可以逆转上皮向间质转化（EMT），涉及受损的肾小管上皮细胞， 导致成纤维细胞的积累。此外，BMP-7还诱导骨髓中的表型变化， 肾成纤维细胞类似于间充质到上皮的转变，再生上皮细胞。该研究旨在 在本申请中提出的这些方法的中心是测试成纤维细胞在肾损伤修复中的潜在作用。 他们试图在分子水平上进一步分析初步的表型观察结果。

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.