Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human Kidney

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PROJECT SUMMARY: The mission of the proposed Kidney Precision Medicine Project Tissue Interrogation Site (TIS) is to apply a platform of integrated multiomic imaging and spatially resolved molecular technologies to biopsies from patients with acute kidney injury (AKI) and chronic kidney disease (CKD) to define key pathways and understand the molecular drivers of disease heterogeneity. This TIS will leverage the unique resources of the Mass Spectrometry Research Center and VU Biomolecular Imaging Center, as well as the world-class clinical environment of the Vanderbilt University Medical Center, the valuable input of our patient partner, and the advanced biocomputational infrastructure available through the data analysis laboratories at Vanderbilt University and the Delft University of Technology. The main objectives of our TIS are to: (1) generate high quality images of kidney biopsies using an innovative state-of-the-art multimodal imaging pipeline that includes matrix- assisted laser desorption/ionization imaging mass spectrometry (IMS), autofluorescence, and stained microscopy; (2) acquire spatially resolved proteomics and transcriptomics data using microLESA, laser capture microdissection, and the GeoMx Digital Spatial Profiler as well as perform network and enrichment analysis to validate and enhance biological interpretation of the imaging data; and (3) implement advanced data analysis strategies to identify potential biomarkers and optimal points of therapeutic intervention. With this suite of technologies, data analysis capabilities, and previous experience developing atlases of healthy-for-age human kidney tissue, we will create kidney tissue atlases to define the molecular landscape of biopsies from various patient populations (e.g., age, race, sex) as well as of AKI and CKD clinical phenotypes, disease states, and transitions; with an eye toward determining potential disease subclasses. To accomplish these aims, we assembled a highly interactive and established team of investigators consisting of complementary expertise in nephrology, cell biology, analytical chemistry, and data science.