Core B: Preclinical Models Core

PROJECT SUMMARY / ABSTRACT: PCMC The PCMC will serve as a central repository for generation, propagation, and characterization of patient-derived organoids (PDOs) from both normal and colorectal cancer (CRC) tissue, as well as isolation of innate immune and participant-matched cytotoxic CD8+ T cells. The PCMC will provide technical expertise to conduct key experiments using these resources. The PCMC will provide support to all three projects within this GI SPORE application and interact closely with the Tissue Pathology and Cellular Analysis Core (TPCA) and the Biostatistics and Bioinformatics Core (BBC). The PCMC is established to support this GI SPORE application in developing and testing novel therapeutic strategies to treat CRC using physiologically relevant complex PDO models. The PCMC will utilize its extensive expertise in PDO methodologies to establish and characterize complex models that recapitulate various aspects of CRC tumors and their microenvironment that includes stromal and immune cells. The overarching goal will be to validate molecular targets of therapeutic strategies developed by the Projects in a preclinical setting using PDOs that include relevant fibroblast and immune cell types. The PCMC will coordinate efforts, consolidate resources, and share experimental expertise by pursuing three Specific Tasks: 1) Generate, maintain, and characterize the CRC PDO biobank; 2) Provide expertise and resources to generate or establish epithelial-only PDO cultures as well as additional complex models, including air-liquid-interface (ALI) cultures and PDOs derived by fine-needle-aspiration (FNA), which self-organize in vitro with multiple stromal/immune cell types; and 3) Provide technical expertise for differentiating colonic PDO models. The immediate goal of the PCMC is to provide support to all three of our projects and the TPCA and BBC. Core personnel will work closely with project and other core leaders to ensure effective support and two-way communication. The longer-term goal of the PCMC is the wider dissemination of these resources and expertise to provide relevant preclinical models that serve as a precision-medicine platform for treatment of CRC patients.