Biology and therapy of C11orf95-RELA fusion-driven ependymoma

C11orf95-RELA 融合驱动的室管膜瘤的生物学和治疗

• 批准号: 10394666
• 负责人: ERIC C. HOLLAND
• 金额: $ 4.12万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394666
• 关键词: Biology; Cell Nucleus; Chimeric Proteins; Chromosome 11; Core Grant; Ependymoma; Event; Fusion Protein Expression; Gene Fusion; Genetic; Genetic Engineering; Goals; Human; Immunology; Modeling; Oncogenes; Oncogenic; Pathway interactions; Phase; RELA gene; Research Project Grants; Supratentorial; System; Systems Biology; Testing; Therapeutic; Therapeutic Effect; chromothripsis; data sharing; data visualization; mouse model; novel; parent grant; pre-clinical; single cell analysis; small molecule; stem cells; tumor; tumor microenvironment; tumorigenesis

ABSTRACT/SUMMARY – OVERALL (HOLLAND) Due to a chromothripsis event on chromosome 11, the majority of supratentorial ependymomas generate and express the gene fusion C11orf95-RELA fusion (RELAFus). The goal of the U54 titled “Biology and therapy of C11orf95-RELA fusion-driven ependymoma is to understand the biology of this fusion protein and the two components that make up the fusion and determine the requirements for continued expression of this fusion protein and what pathways downstream are critical for oncogenesis. We will use a combination of novel mouse models and human neuro stem cell systems with readouts of single cell analysis, immunology, tumor microenvironment, systems biology, and data visualization. In addition to the administrative core, the grant has three main Projects, a data visualization and sharing core. The research projects include, Project 1) Mechanisms and models of C11or95 and C11or95-RELA fusions (RELAFus), Project 2) Genetic interrogation of therapeutic vulnerabilities for C11orf95-RELA fusion, and Project 3) Identifying small molecules with therapeutic effects in RELAFus -driven EPN and testing them in preclinical genetically engineered models of EPN.

摘要/摘要 - 总体（荷兰） 由于染色体11上的染色体事件，大多数superatorial sendentorial会产生和 表达基因融合C11orf95-Rela融合（relafus）。 U54的目标是“生物学和疗法 C11ORF95-RELA融合驱动的转心瘤是为了了解该融合蛋白的生物学和两个 组成融合并确定持续表达此融合的要求 蛋白质以及下游的途径对于肿瘤发生至关重要。我们将结合新颖的鼠标 模型和人类神经干细胞系统，具有单细胞分析，免疫学，肿瘤的读数 微环境，系统生物学和数据可视化。除了行政核心外，赠款还有 三个主要项目，一个数据可视化和共享核心。研究项目包括项目1）机制 以及C11or95和C11or95-Rela融合（Relafus）的模型，项目2）治疗的遗传审查 C11orf95-Rela融合的脆弱性和项目3）识别具有治疗作用的小分子 Relafus驱动的EPN并在EPN的临床前一般工程模型中对其进行测试。