The USC (Re)Building the Kidney Coordinating Center

 描述(申请人提供)：哺乳动物肾脏的功能单位是肾单位--一种复杂的复合结构，由一个具有紧密联系的特殊血管网络的上皮肾小管组成。肾单位起源于仅存在于胎儿时期的肾源性干细胞/祖细胞群体。因此，所有的肾单位都是在出生前形成的。此后，在急性和可能的慢性损伤发作后，恢复现有的肾单位结构是器官修复肾脏的内在策略。通过对非人类模型系统的研究，我们对肾脏发育过程中发挥作用的分子和细胞过程有了一个大致的框架，并对维持正常肾脏功能的内在修复过程产生了理解。不幸的是，正常的修复过程是不够的：1,000,000名患者目前被诊断为终末期肾病(ESRD)，其中约400,000人正在接受透析，平均5年存活率为38%。对于终末期肾病患者来说，除了透析之外，唯一的选择是肾脏移植，但移植的数量--大约20000例/年--与患者的需求不匹配。(重新)建立肾脏联盟的长期目标是利用我们对肾单位发育和修复的知识来打造治疗肾脏损伤和疾病的创新方法。该联盟正在制定的基本论点是，由几个小组协调、专注、适应和互动的研究方案有可能在一个时间框架内产生结果，而通过静态收集独立的单一研究人员赞助的研究项目是不可能的。整个研究联盟之间的协调要求能够快速整合新的研究项目，交流结果，并在整个联盟内共享知识和数据。在研究结束时公布结果是不够的，相反，必须能够在研究过程的所有阶段逐步分享。为了解决这些问题，我们提议建立一个重建肾脏协调中心(RBKC)，以确保联盟作为一个协调的研究网络有效运作，最大化单个项目的价值，并将联盟的活动传达给广泛的研究社区。具体地说，RBKC的目标是：1)创建组织结构和流程，使RBKC研究人员、NIDDK和更广泛的研究社区之间能够进行无缝和频繁的交流与合作；2)创建数据门户，使不断变化的研究人员集合能够快速创建、分析、共享和发现各种类型的数据；3)扩大研究社区，通过建立和管理机会池计划，为有针对性的短期研究结果创建一个框架；4)将联盟的成果传播给更广泛的研究社区。总体而言，RBKC的这些要素的影响将加快财团内部和更广泛社区的发现速度。

 DESCRIPTION (provided by applicant): The functional unit of the mammalian kidney is the nephron - a complex, composite structure comprising an epithelial renal tubule with a closely associated specialized vascular network. Nephrons arise from a nephrogenic stem/progenitor population that only exists during fetal life. Consequently, the entire complement of nephrons is formed prior to birth. Thereafter, restoration of existing nephron structures is the organ's intrinic strategy for kidney repair following acute, and likely chronic, injury episodes. From studies in non-human model systems, we have a general framework for the molecular and cellular processes at play during kidney development and an understanding is emerging of intrinsic repair processes that maintain normal kidney function. Unfortunately, normal repair processes are inadequate: 1,000,000 patients are currently diagnosed with end state renal disease (ESRD), approximately 400,000 of these are on dialysis with a mean 5-year survival rates of 38%. The only option beyond dialysis for the ESRD patient is kidney transplant, but the number of transplants - approximately 20,000/year - does not match patient need. The long-term goal of the (Re)Building the Kidney Consortium is to harness our knowledge of nephron development and repair to forge innovative new approaches to treat injury and disease of the kidney. The consortium is being developed with the underlying thesis that a coordinated, focused, adaptive and interactive program of research by several groups has the potential to yield results in a timeframe that would not be possible through a static collection of independent single investigator sponsored research projects. Coordination across the research consortium demands the ability to rapidly integrate new research projects, communicate results, and share knowledge and data across the consortium. It is not enough to publish results at the end of a study, but rather, it must be possible to incrementally share at all stages of the research process. To address these issues, we propose to create a ReBuilding the Kidney Coordinating Center (RBKC) to ensure the consortium operates effectively as a coordinated research network, maximizing the value of individual projects, and communicates consortium activities to the broad research community. Specifically, the RBKC aims to: 1) create organizational structure and processes that will enable seamless and frequent communication and collaboration between RBKC researchers, the NIDDK and the broader research community, 2) create a data portal that will empower changing collections of researchers to rapidly create, analyze, share and discover diverse types of data, 3) broaden the research community and create a framework for targeted shorter term research results by establishing and managing an opportunity pool program, 4) disseminate consortium results to the broader research community. In total, the impact of these elements of the RBKC will accelerate the rate of discovery within the consortium and by the broader community.