Normal & Neoplastic Growth in the Brain

普通的

• 批准号: 7627880
• 负责人: SUZANNE J BAKER
• 金额: $ 195.31万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627880
• 关键词: Normal; Neoplastic; Growth; Brain

`DESCRIPTION (provided by Project Leader): Brain tumors are the most common group of solid malignancies in children, causing devastating mortality and morbidity in a very understudied patient population. The goal of this program project is to improve understanding and treatment of pediatric brain tumors. During the first funding period, Project leaders worked together to develop novel mouse models that provided key biological insights into cerebellar growth regulation and medulloblastoma development, used these models for relevant preclinical testing of new therapeutic agents, and translated research results into clinical trials. The current application expands the focus of the program to encompass additional pediatric brain tumors. Five interactive projects plan directed studies of growth regulation in the brain using human tumors and mouse models to study signal transduction, gene expression and function in the context of pediatric brain tumors and brain development. An Administrative Core, a Bioinformatics and Biotechnology Core and a Neuropathology Core provide essential support to all projects. In Project 1, S. Baker investigates the molecular pathogenesis of pediatric high-grade glioma taking advantage of a large collection of primary tumors and novel mouse models for glioma that she developed. In Project 2, T. Curran investigates the mechanism of action of a small molecule inhibitor of Hedgehog signaling that he showed ablated medulloblastoma in his model systems. In Project 3, R. Gilbertson will define molecular subgroups of medulloblastoma through analysis of human tumors and development of mouse models, and will characterize cancer stem cells and their niches in subclasses of medulloblastoma. In Project 4, P. McKinnon will further his analysis of defective DNA damage response underlying brain tumor development and will determine the effects of DNA repair inhibitors as a therapeutic approach for brain tumors. In Project 5, M. Roussel and C. Sherr will explore mechanisms of oncogenic transformation in medulloblastoma, and will define microRNAs that modulate gene expression in cerebellar development and medulloblastoma. Integrated analyses within the group will identify common and unique signal transduction pathways in pediatric brain tumorigenesis.

‘描述(由Project Leader提供)：脑瘤是儿童中最常见的实体恶性肿瘤，在研究很少的患者群体中造成毁灭性的死亡和发病率。该计划项目的目标是提高对儿童脑肿瘤的认识和治疗。在第一个资助期，项目负责人共同开发了新的小鼠模型，为小脑生长调节和髓母细胞瘤的发展提供了关键的生物学见解，将这些模型用于新治疗药物的相关临床前测试，并将研究成果转化为临床试验。目前的应用扩大了该计划的重点，涵盖了更多的儿科脑瘤。五个互动项目计划使用人类肿瘤和小鼠模型指导对大脑生长调节的研究，以研究儿童脑瘤和脑发育背景下的信号转导、基因表达和功能。行政核心、生物信息学和生物技术核心以及神经病理学核心为所有项目提供必要的支持。在项目1中，S.Baker利用她开发的大量原发肿瘤和新的胶质瘤小鼠模型，研究了儿童高级别胶质瘤的分子发病机制。在项目2中，T.Curran研究了Hedgehog的一种小分子抑制剂的作用机制，他在他的模型系统中显示了髓母细胞瘤的消融信号。在项目3中，R.Gilbertson将通过分析人类肿瘤和发展小鼠模型来定义髓母细胞瘤的分子亚群，并将在髓母细胞瘤的亚类中表征癌症干细胞及其利基。在项目4中，P.McKinnon将进一步分析导致脑瘤发生的缺陷DNA损伤反应，并将确定DNA修复抑制剂作为脑瘤治疗方法的效果。在项目5中，M.Roussel和C.Sherr将探索髓母细胞瘤的致癌转化机制，并将定义在小脑发育和髓母细胞瘤中调节基因表达的microRNAs。该小组内部的综合分析将确定儿科脑肿瘤发生中常见和独特的信号转导途径。