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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.

项目总结实验模型核心负责管理、跟踪、质量控制和分发所有胶质母细胞瘤(GBM)动物模型(患者来源的异种移植(PDX)模型，PDX来源的有机化合物，同基因小鼠和基因工程小鼠)，用于所有项目的实验研究和来自人类的生物标本用于跨多个机构进行验证。核心还将负责从这些模型，对于小鼠肿瘤的双光子体内成像，以及对于单细胞和空间转录 P01的技术资源。一套&gt；180 PDX GBM模型和&gt；5同基因小鼠模型基因组图谱(DNA、RNA测序)可用于项目的假设检验。人体标本证实小鼠模型的发现将有助于验证性别差异，尽管将人类患者与老鼠模型进行比较是一个警告。核心加强项目和P01通过协调用于实验研究的模型的分布，其中肿瘤细胞的性别是通过性基因特异性聚合酶链式反应和性染色体核型鉴定。试验性项目的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，然后部署同基因和基因工程小鼠胶质瘤模型，患者来源异种GBM模型、短期GBM培养和有机物，提供高质量、科学相关的使用标准化的收集、质量控制、储存/跟踪和分发向P01调查人员提供生物检疫根据批准的IACUC指南，以及2)制造高质量的、具有科学相关性的临床生物检验品通过不断努力和创新，向P01调查人员提供标准化收集、质量控制(包括集中的神经病理检查)、存储/跟踪和在适当的人类环境下分发使用安全、易于访问的数据库的主题(OHRP)监管指南。一个明确的好处是实验模型核心是跨所有项目共享使用模型的协调和可见性，共享质量控制、批次(或通过)效应、生长特性、基因组图谱和跨项目共享实验结果的数据。