Project Summary/Abstract: Overall Component The Washington University Chronic Kidney Disease National Resource Center is focused on the significant problem of chronic kidney disease (CKD), which affects almost 15% of the US population and carries significant morbidity and mortality. Several scientific advances have the promise to accelerate CKD research, but many of these advances are not accessible to the kidney research community due to limited expertise and/or the need for expensive equipment. Thus, this NRC will address the fundamental challenge of providing better access to cutting-edge techniques in single cell omics, genetics, and metabolism to the kidney research community to facilitate advances in CKD research. Dr. Ben Humphreys is the overall program director, and this Center will consist of four Cores: an Administrative Core, two Biomedical Resource Cores, and a Resource Development Core. The Administrative Core will oversee distribution of funds across the Cores, communicate with the National O’Brien Consortium, manage the Summer Student Enrichment Program, and promote the involvement of early stage investigators and a diverse workforce. The Variant Validation Core, one of the Biomedical Resource Cores, investigates the pathogenicity of genetic variants of uncertain significance using CRISPR/Cas9-gene editing, in silico approaches, and tailored in vitro assays. The Metabolism Core, the other Biomedical Resource Core, provides consultation for users and access to a number of metabolic assays to interrogate changes in kidney metabolism relevant to CKD. These assays include Seahorse bioflux analysis, radioactive substrate oxidation assays of tissue ex vivo, untargeted metabolomics, and stable isotope tracer studies. The Metabolism Core will also work with the O’Brien Consortium to provide validated protocols for assays commonly performed (e.g. Seahorse assays on primary cells) and provide hands’ on training using these protocols. The Single Cell Omics Research Evolution (SCORE) Core is the Resource Development Core, which develops protocols and bioinformatics pipelines for cutting-edge techniques like split pool barcoding for single nuclei multi-omics and high resolution in-situ sequencing-based spatially resolved transcriptomics. All four Cores will work together and with the network of O’Brien National Resource Centers to make scientific advancements more accessible to the kidney research community with particular emphasis on junior investigators and development of a diverse biomedical workforce.

Project Narrative The Washington University Chronic Kidney Disease National Resource Center aims to improve resources available to the chronic kidney disease research community. This Center will provide a mechanism to test the pathogenicity of genetic variants of uncertain significance, resources to interrogate metabolism in vitro and in vivo, and an incubator space to further develop single cell omics technologies. A key objective is to share these resources with the larger O’Brien consortium and kidney research community to enhance research on the pathophysiology of chronic kidney disease.