Project Summary/Abstract - Molecular Imaging Core The overarching goal of the Molecular Imaging Core is to provide full-service assistance in the interrogation and analysis of experimental animal and human-derived kidney tissue. This goal will be accomplished through the conduct of the following specific aims: 1) Provide the renal research community with three high impact services: Co-Detection by Indexing (CODEX), Large-scale 3D imaging and Tissue Cytometry (3DTC), and spatial transcriptomics (ST) and 2) Provide analytic support to ensure the outputs of molecular imaging are interpretable and integrated within and across technologies, and data outputs are consistent with best practices and are harmonized with cell-type and state definitions used across the renal community. The technologies can be offered individually to facilitate spatial anchoring of proteomic and transcriptomic signals, or offered together on the same tissue specimen. An integrated output can be accomplished by direct co- registration on consecutive sections or alignment in the analytical space. The analytical support provided will allow investigators to test hypotheses and create a common framework for cell type and state annotation across multiple NIDDK initiatives. Together, the technologies offered through the Molecular Imaging Core will allow investigators to define, localize, and quantify: 1) all cell populations, 2) cell-cell interactions within 3D neighborhoods, 3) morphological changes and injury regions, 4) the expression of 18,000 genes mapped over histopathology, and 5) deep immune and injury phenotypes anchored spatially. Such outputs provide a unique and powerful service to the renal community. The proposed research is significant, because it is expected to aid the renal community in identifying critically needed biomarkers of disease progression, optimizing preclinical studies, and developing specific and targeted therapeutic interventions for a wide range of kidney diseases.