Core C: Experimental Models

核心 C：实验模型

基本信息

批准号：
10023719
负责人：
MICHAEL E. BERENS
金额：
$ 58.95万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-14 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10023719
关键词：
Animal Model Astrocytes Behavior Blood Brain Neoplasms Cells Characteristics Clinic Clinical Data Collection DNA Data Databases Dominant-Negative Mutation Electroporation Engineering Event Experimental Models FTH1 gene Female Four Core Genotypes Freezing Generations Genes Genetic Genetically Engineered Mouse Glioblastoma Glioma Goals Gonadal Steroid Hormones Growth Guidelines H ferritin Heterogeneity Human IACUC Implant Individual Informatics Infrastructure Institution Institutional Review Boards Iron Karyotype determination procedure Knock-out Knockout Mice LCN2 gene Label Modeling Mus Neurofibromatosis 1 Organoids Outcome Paraffin Pathology Patients Performance Ploidies Population Pre-Clinical Model Preclinical Testing Quality Control Reporter Research Personnel Resources Secure Services Sex Chromosomes Sex Differences Specimen Standardization TP53 gene Technology Testing Testis Tissue Banks Tissues Treatment outcome Tumor Cell Line Universities University Hospitals Validation Xenograft Model Xenograft procedure Y Chromosome autosome base biobank cancer imaging cell transformation clinically relevant cost effective data sharing experimental study genomic profiles human subject human tissue imaging platform in utero in vivo in vivo imaging in vivo two-photon imaging innovation junctional adhesion molecule male model development mouse model neoplastic cell pathology imaging quality assurance radiological imaging response sex sry Genes transcriptome sequencing transcriptomics tumor microenvironment two photon microscopy

项目摘要

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.

项目概要实验模型核心负责所有模型的策划、跟踪、质量控制和分发胶质母细胞瘤 (GBM) 动物模型（患者来源的异种移植 (PDX) 模型、PDX 衍生的类器官、同基因小鼠和基因工程小鼠）用于所有项目的实验研究和人类生物样本以便在多个机构之间进行验证。核心还将负责生成类器官这些模型用于小鼠肿瘤的双光子体内成像，以及单细胞和空间转录组学 P01 的技术资源。一套 >180 个 PDX GBM 模型和 >5 个同基因小鼠模型基因组分析（DNA、RNA 测序）可用于项目的假设检验。人体标本确认小鼠模型的发现将有助于验证性别差异，尽管不同性别之间存在先天异质性与小鼠模型相比，人类患者是一个警告。核心强化项目和P01 协调实验研究模型的分布，其中肿瘤细胞的性别通过性基因特异性 PCR 和性染色体核型分析进行表征。实验目标模型核心将通过以下具体目标来实现： 1) 创建、组织和维护基础设施，然后部署源自患者的同基因和基因工程小鼠神经胶质瘤模型异种移植 GBM 模型、短期 GBM 培养物和类器官，提供高质量、科学相关的使用标准化采集、质量控制、存储/跟踪和分发向 P01 研究人员提供生物样本根据批准的 IACUC 指南，以及 2) 制作高质量、科学相关的临床生物样本通过在标准化收集、质量方面的持续努力和创新，P01 研究人员可以使用控制（包括集中神经病理学审查）、存储/跟踪和在适当的人力下分发使用安全、易于访问的数据库的主题（OHRP）监管指南。的决定性好处实验模型核心是所有项目中模型共享使用的协调和可见性，共享质量控制、批次（或传代）效应、生长特征、基因组分析和跨项目实验结果的数据共享。