Core C: Experimental Models

核心 C：实验模型

基本信息

批准号：
10653109
负责人：
MICHAEL E. BERENS
金额：
$ 54.82万
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 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10653109
关键词：
Animal Model Astrocytes Behavior Blood Brain Neoplasms Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing 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 Genomics 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 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 procedure Y Chromosome autosome base biobank cancer imaging cell transformation clinically relevant cost effective data sharing experimental study 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 neuropathology pathology imaging patient derived xenograft model quality assurance radiological imaging response sex sry Genes tissue fixing 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.

项目摘要实验模型核心负责所有所有人的策划，跟踪，质量控制和分布胶质母细胞瘤（GBM）动物模型（患者衍生的异种移植物（PDX）模型，PDX衍生的类器官，Syngeneic 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测量的实验研究用于跨多个机构的验证。核心还将负责从这些模型，用于小鼠肿瘤的两光体成像，以及单细胞和空间转录组学作为 P01的技术资源。一套> 180个PDX GBM型号和> 5个合成小鼠模型的套件基因组分析（DNA，RNA测序）可用于项目的假设检验。人类标本为了确认鼠标模型的发现将有助于验证性别差异，尽管与小鼠模型相比，人类患者是一个警告。核心加强了项目和P01 协调肿瘤细胞性别的实验研究模型的分布通过性别基因特异性PCR和性染色体核分型的特征。实验的目标模型核心将通过以下特定目的完成：1）创建，组织和维护基础架构，然后部署合元和基因工程的小鼠神经胶质瘤模型，患者衍生异种移植GBM模型，短期GBM培养物和器官，提供高质量，科学相关的使用标准化收集，质量控制，存储/跟踪和分发的P01研究人员的生物测量根据批准的IACUC指南，2）制作高质量的科学临床生物测量 P01调查人员可以通过持续的努力和标准化收集，质量的创新控制（包括集中式神经病理审查），在适当人类中的存储/跟踪和分布使用安全，易于访问的数据库的主题（OHRP）监管指南。确定的好处实验模型核心是所有项目中共享模型共享使用的协调和可见性，共享质量控制，批次（或通过）效果，生长特征，基因组分析和跨项目来自实验结果的数据共享。