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.
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. The long-term goal of the (Re)Building the Kidney Consortium (RBKC) is to harness our knowledge of nephron development and repair to forge innovative new approaches to treat injury and disease of the kidney. The RBKC 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. We propose to create a Rebuilding the Kidney Coordination Center whose objective is to facilitate the process of melding the individual projects of the RBKC into an integrated consortium, to build a comprehensive research community through an evolving set of 'opportunity pool' studies and to accelerate the pace of research through platform for rapid sharing and access of data.
|Menon, Rajasree; Otto, Edgar A; Kokoruda, Austin et al. (2018) Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney. Development 145:|
|Lindström, Nils O; Guo, Jinjin; Kim, Albert D et al. (2018) Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney. J Am Soc Nephrol 29:806-824|
|Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy et al. (2018) Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis. Dev Cell 45:651-660.e4|
|Gupta, Navin; Susa, Koichiro; Yoda, Yoko et al. (2018) CRISPR/Cas9-based Targeted Genome Editing for the Development of Monogenic Diseases Models with Human Pluripotent Stem Cells. Curr Protoc Stem Cell Biol 45:e50|
|Tögel, Florian; Valerius, M Todd; Freedman, Benjamin S et al. (2017) Repair after nephron ablation reveals limitations of neonatal neonephrogenesis. JCI Insight 2:e88848|
|Czajkowski, Karl; Kesselman, Carl; Schuler, Robert (2017) ERMrest: A Collaborative Data Catalog with Fine Grain Access Control. Proc IEEE Int Conf Escience 2017:510-517|
|Uzarski, Joseph S; DiVito, Michael D; Wertheim, Jason A et al. (2017) Essential design considerations for the resazurin reduction assay to noninvasively quantify cell expansion within perfused extracellular matrix scaffolds. Biomaterials 129:163-175|
|Bugacov, Alejandro; Czajkowski, Karl; Kesselman, Carl et al. (2017) Experiences with Deriva: An Asset Management Platform for Accelerating eScience. Proc IEEE Int Conf Escience 2017:79-88|
|Adam, Mike; Potter, Andrew S; Potter, S Steven (2017) Psychrophilic proteases dramatically reduce single-cell RNA-seq artifacts: a molecular atlas of kidney development. Development 144:3625-3632|
|Finch, Caleb E; McMahon, Andrew P (2016) Stem cells for all ages, yet hostage to aging. Stem Cell Investig 3:11|