Core C: Experimental Models

点击翻译按钮获取中文摘要

PROJECT SUMMARY The Experimental Models Core is responsible for curation, tracking, quality control, and distribution of all glioblastoma (GBM) animal models (patient-derived xenograft (PDX) models, PDX-derived organoids, syngeneic mouse and genetically engineered mice) for experimental studies in all Projects and biospecimens from humans for validation across multiple institutions. The Core will also be responsible for the generation of organoids from these models, for two-photon in vivo imaging of tumors in mice, and for single cell and spatial transcriptomics as technology resources for the P01. A suite of >180 PDX GBM models and >5 syngeneic mouse models with genomic profiling (DNA, RNA sequencing) are available for hypothesis testing by the projects. Human specimens to confirm findings from mouse models will help validate sex differences, albeit the innate heterogeneity across human patients compared to mouse models is a caveat. The core strengthens the projects and the P01 by coordinating the distribution of models for experimental studies in which the sex of the tumor cells are characterized via sex gene-specific PCR and sex chromosome karyotyping. The goals of the Experimental Models Core will be accomplished through the following specific aims: 1) To create, organize, and maintain infrastructure, then deploy syngeneic and genetically engineered mouse glioma models, patient-derived xenograft GBM models, short-term GBM cultures and organoids, providing high-quality, scientifically relevant biospecimens to P01 investigators using standardized collection, quality control, storage/tracking and distribution under approved IACUC guidelines, and 2) To make high-quality, scientifically-relevant clinical biospecimens available to the P01 investigators through continued efforts and innovations in standardized collection, quality control (including centralized neuro pathology review), storage/tracking and distribution under proper human subject (OHRP) regulatory guidelines using secure, readily accessible databases. A decided benefit of the Experimental Models Core is the coordination and visibility of shared use of models across all Projects, with shared quality control, batch (or passage) effects, growth characteristics, genomic profiling, and cross-Project data sharing from the experimental outcomes.