Core 1: Biospecimens Core

核心 1：生物样本核心

• 批准号: 10729278
• 负责人: Jann N. Sarkaria
• 金额: $ 34.82万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729278
• 关键词: Animal Experiments; Animal Model; Animals; Archives; Biological; Biological Models; Brain; Brain Neoplasms; Categories; Cells; Clinic; Clinical Trials; Collaborations; Collection; Complex; Coupled; Ensure; Future; Genetically Engineered Mouse; Glioblastoma; Goals; Human; Immunologics; Intracranial Neoplasms; Laboratories; Modeling; Neurons; Neurosurgeon; Organoids; Patients; Pilot Projects; Research Project Grants; Research Support; Resources; Retrieval; Sampling; Scientist; Signal Transduction; Slice; Specimen; System; Systems Analysis; Systems Biology; Tissues; Translations; Work; Writing; bench to bedside; biobank; biological specimen archives; clinically relevant; design; experience; experimental study; image registration; in vivo; neoplastic cell; neuro-oncology; patient derived xenograft model; pharmacologic; pre-clinical; preclinical study; prospective; quality assurance; tumor; tumor microenvironment

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

摘要 – 生物样本核心 生物样本核心将作为协调提供高度转化的中心资源 用于主要研究项目和可能的几个研究项目的相关动物和人类分析标本 预期的试点项目最大限度地提高对动物进行的分析的翻译相关性。 标本、患者来源的异种移植物（PDX）和基因工程小鼠模型（GEMM） 胶质母细胞瘤（GBM）将用于我们的临床前研究，我们在使用这些模型方面拥有丰富的经验。 用于评估颅内肿瘤的系统生物学以及药理操作如何失调 结合这些临床前研究、操作分析。 GBM 患者的标本为进行的生物建模提供了“基本事实”。 生物样本核心将利用与 DFCI 和 DFCI 的神经外科医生建立的合作关系 梅奥诊所 (Mayo Clinic) 和梅奥诊所 (Mayo Clinic) 提供的广泛的神经肿瘤生物库可提供存档的数据 肿瘤样本和图像配准的新鲜手术标本的前瞻性分析， 来自动物和人类生物样本的类器官和组织切片培养物也将用于实现 逆向转化关键发现并进一步完善或验证我们的系统分析。 跨两个项目对相同生物样本进行协调分析的机会，科学 经理将协调生物样本的采集、质量保证审查、运输和分析 核心部门还将确保适当的监管审查和批准到位。 支持动物和人类生物样本的收集和分析 核心的总体工作。 可分为两个目标，支持动物和人类 GBM 研究。 具体目标 1：开发、管理和执行荷瘤动物体内研究 具体目标 2：协调人类生物样本的收集和分发