The Recruitment Sites recruit adult men and women with either AKI or CKD for longitudinal cohort studies that include a research kidney biopsy. The Recruitment Sites work collaboratively to capture demographic information, conduct longitudinal clinical phenotyping, and collect biological samples in a standardized manner.
Tissue Interrogation Sites receive kidney biopsy tissue collected from participants at the Recruitment Sites. They use this tissue to:
We are applying and integrating several complementary technologies to create a complete catalog of molecular signatures of all kidney cell types in 3D space: two novel single-cell technologies to mature archived (frozen) human kidney specimens; a single-nucleus (sn) transcriptomic profiling method (snRNA-seq); and a 3D in situ RNA mapping method (DART-FISH).
With our combined expertise we have developed a spatial metabolomics approach to identify metabolites in human kidneys, employing ultra-high mass resolution MS imaging for tissue analysis and a bioinformatics resource (METASPACE) to annotate metabolites for anatomical localization and 3-D reconstruction.
This allows us to understand the major metabolic pathways that initiate and cause progression of disease in patients with AKI and CKD.
We are seeking to interrogate gene expression in the kidney at the single cell level, defining cell-type and disease-state-specific gene expression profiles, with accompanying two and three-dimensional spatial characterization (cell-cell and cell-matrix relationships).
This approach allows us to understand the roles of the individual renal cell types in their cellular and disease context, which is critical to developing novel targeted therapies.
Our labs have developed two multiplex assays (multiplex Immunofluorescence and In Situ Hybridization (mIFISH) and CODEX) that visualize multiple mRNAs and proteins at single cell resolution level.
These assays, coupled with advanced high resolution whole slide imaging and sophisticated computer-assisted image analysis, can assess not only the quantitative aspects but also the spatial organizational aspects of the analytes.
The in situ assays will be supplemented by additional ancillary tissue-based assays of near single cell proteomics and multiplexed single-cell RNA-Seq (mdrosc RNA-Seq).
Our site will initially integrate large-scale 3D tissue imaging for quantitative supervised and unsupervised analysis/cytometry with sub-segmental “omics” data on the same kidney biopsy specimen. The sub-segmental “omics” pipeline will isolate specific kidney nephron segments and interstitial/other targeted areas for downstream analysis with transcriptomics and proteomics.
The omics analysis will be eventually expanded to include epigenetics. This approach will complement other interrogation techniques within KPMP by providing tissue context and increasing spatial resolution for molecular signatures that arise in heterogeneous areas during kidney disease.
The Central Hub is responsible for aggregating, analyzing, and visualizing the generated data and providing scientific, infrastructure, and administrative support for the KPMP consortium. The Central Hub houses the Data and Sample Coordinating Center (DCC), the Data Visualization Center (DVC), and the Administrative Core (AC).
The KPMP recognizes that it must collaborate with the broader research community to fully achieve these objectives. Thus, the KPMP Central Hub (CH) will administer an “Opportunity Pool” to facilitate the formation of new partnerships.
The Steering Committee (SC) will be the primary governing body for all KPMP scientific activities. The SC will coordinate all sites awarded under these FOAs. The voting membership of the SC will include: one PD/PI from each award made under this and the companion FOAs, the NIH PS, and a representative from the Patient Engagement Working Group of the CH. The Chair of the SC will be assigned by NIH Program Staff, and may be chosen from outside the KPMP. Face-to-face meetings of this committee will occur at least two times a year. A portion of the SC meeting may be open to the public.
The SC will be the primary governing body for all of the KPMP scientific activities. The SC will coordinate all projects awarded under the KPMP FOAs.
The role of the Steering Committee includes:
Voting may occur electronically, in-person, or via teleconferences. There are a total of 14 Steering Committee votes. Each grant is allotted one vote, regardless of the number of PIs associated with the grant. NIDDK has one vote, and the SC patient representative has one vote.
(last updated July 3rd, 2019)
Chair: Jonathan Himmelfarb (University of Washington)
The following members are allowed to vote on behalf of their grant/affiliation. Only one vote may be cast per affiliation.
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