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 生物标本核心将作为一个中心资源，协调提供高度预防性的 相关的动物和人类分析标本，用于两个主要的研究项目和可能的几个 预期的试点项目。最大限度地提高动物分析的翻译相关性 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物操作如何失调 这些系统中的关键信令节点。结合这些临床前研究，分析手术 来自GBM患者的标本为所进行的生物建模提供了“基础事实”。在这一背景下， 生物标本核心将利用与DFCI和 马约诊所和马约诊所提供的广泛的神经肿瘤生物库， 肿瘤样本和图像配准的前瞻性分析，新鲜手术标本。衍生细胞， 来自动物和人类生物标本的类器官和组织切片培养物也将用于使 对关键发现进行逆向翻译，并进一步完善或验证我们的系统分析。为了利用 在两个项目中协调分析相同生物样本的机会， 经理将协调生物样本采集、质量保证审查、运输和分析。 实验室和项目。核心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标本的采集和分析。核心小组的总体努力 可以分为两个目的，以支持动物和人类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：协调人体生物标本的采集和分发