Functional Dissection of the K27M Histone Mutation in Vivo

体内 K27M 组蛋白突变的功能解析

• 批准号: 9337512
• 负责人: Oren Josh Becher
• 金额: $ 14.1万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-10 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337512
• 关键词: Alpha Cell; Astrocytes; Biology; Brain Neoplasms; Brain Stem; Brain Stem Glioma; Brain Stem Neoplasms; Cause of Death; Cell Proliferation; Cells; Child; Childhood Brain Neoplasm; Clinical Trials; Complex; Development; Diffuse intrinsic pontine glioma; Disease; Dissection; Dorsal; Foundations; Gene Targeting; Genes; Genetic; Genetically Engineered Mouse; Glial Fibrillary Acidic Protein; Gliomagenesis; Goals; Histone H3; Histones; Human; In Vitro; Independent Scientist Award; Laboratories; Location; Malignant Neoplasms; Malignant neoplasm of brain; Modeling; Molecular Profiling; Mus; Mutation; Neonatal; Pathogenesis; Pharmaceutical Preparations; Platelet-Derived Growth Factor; Polycomb; Proto-Oncogene Proteins c-sis; Reporting; Research; Scientist; TP53 gene; Therapeutic Agents; Treatment Efficacy; comparative; design; differential expression; effective therapy; gain of function mutation; in vivo; mouse model; mutant; nerve stem cell; nestin protein; novel; overexpression; progenitor; public health relevance; relating to nervous system; transcriptome sequencing; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable brain tumor that arises in children. My laboratory is one of very few laboratories around the world that is studying DIPG biology using genetically engineered mouse modeling. This Independent Scientist Award will give me the opportunity to focus on research to dissect the mechanisms by which K27M histone mutations contribute to DIPG pathogenesis. Ultimately, this information will lay the groundwork for the identification of effective therapeutic agents to treat this incurable cancer.

描述（申请人提供）：弥漫性内禀脑桥胶质瘤（DIPG）是一种发生于儿童的无法治愈的脑肿瘤。我的实验室是世界上为数不多的使用基因工程小鼠模型研究DIPG生物学的实验室之一。获得独立科学家奖将使我有机会专注于研究K27M组蛋白突变对DIPG发病机制的影响。最终，这些信息将为确定治疗这种无法治愈的癌症的有效药物奠定基础。

项目成果

A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells.

• DOI: 10.1016/j.neo.2015.12.002
• 发表时间: 2016-01
• 期刊: Neoplasia (New York, N.Y.)
• 作者: Misuraca KL;Hu G;Barton KL;Chung A;Becher OJ
• 通讯作者: Becher OJ