Transplant Pathology and Tissue Imaging Core B

SUMMARY For this P01, The Transplant Pathology, Tissue Imaging, Proteomic and Transcriptomics Core (Core B) will play a critical and well-integrated scientific role in supporting the two Projects, with a strong emphasis on the central focus of the Program, that concerns innovative approaches to promote regulatory immune cell function, extend renal allograft survival and allow IS drug withdrawal in rhesus macaques. Project 1 (Thomson) will focus on innovative approaches to promote regulatory dendritic cell (DCreg) function, whereas Project 2 (Ezzelarab) will extend current studies on the potential of novel anti-inflammatory agents to enhance regulatory T cell (Treg) function, extend graft survival and allow IS drug withdrawal in monkeys receiving a similar baseline IS regimen to those in Project 1. Core B will also work in close conjunction with Core A (Administration, Biostatistics and Bioinformatics) and Core C (Nanotechnology) to optimize Program integration and synergy and to achieve the overall objectives of the Research Program. The Specific Aims of Core B are to: Prepare, store, and optimally analyze tissue biopsies using routine histopathologic and protein localization techniques through implementation of digital quantitation of proteins and mRNA in specific regions of interest. 2. Evaluate and report the routine histopathologic diagnoses, recognize trends, and propose subsequent direction for future studies using a variety of innovative analytic techniques, including innovative assessment of sub- pathological rejection (as defined by enhanced colonization of the allograft by effector cells not detectable by routine light microscopy and potential immune synapse formation in kidney allografts) as predictors of safe withdrawal of immunosuppression. 3. Provide technical and professional expertise in the design and implementation of the tissue diagnostic strategies, including digital imaging, image analysis (including tracking of CARTregs), and NGP as needed. 4. Prioritize scheduling of samples, based on histopathological data, in consultation with the PLs and in relation to meeting the objectives of the Research Program.