Core 1: Biospecimens Core

ABSTRACT – BIOSPECIMENS CORE The Biospecimens Core will serve as a central resource to coordinate provision of highly translationally relevant animal and human analytical specimens for use in both main research projects and likely several of the anticipated pilot projects. To maximize the translation relevance of the analyses performed on animal specimens, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs) of glioblastoma (GBM) will be used for our pre-clinical studies. We have extensive experience using these models for evaluating the systems biology of intracranial tumors and how pharmacologic manipulations dysregulate critical signaling nodes within these systems. Coupled with these preclinical studies, analysis of operative specimens from GBM patients provides a ‘ground-truth’ for the biological modeling performed. In this context, the Biospecimens Core will capitalize on established collaborations with neurosurgeons at both DFCI and Mayo Clinic and the extensive Neuro-Oncology Biobank available at Mayo Clinic for provision of both archived tumor samples and prospective analysis of image-registered, fresh operative specimens. Derivative cell, organoid, and tissue-slice cultures from both animal and human biospecimens also will be used to enable reverse translation of key findings and to further refine or validate our systems analyses. To capitalize on opportunities for coordinated analyses of the same biological samples across both Projects, a Scientific Manager will coordinate biospecimen collection, quality assurance review, shipment and analyses across laboratories and projects. The Core also will ensure appropriate regulatory review and approvals are in place to support both the animal and human biospecimen collections and analyses. The overall efforts of the Core can be divided into two Aims to support animal and human GBM studies. Specific Aim 1: Develop, manage, and execute in vivo studies in tumor-bearing animals Specific Aim 2: Coordinate the collection and distribution of human biospecimens