Normal & Neoplastic Growth in the Brain

普通的

• 批准号: 8056135
• 负责人: SUZANNE J BAKER
• 金额: $ 193.24万
• 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/8056135
• 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（由项目负责人提供）：脑肿瘤是儿童最常见的实体恶性肿瘤，在研究非常不足的患者群体中造成毁灭性的死亡率和发病率。该项目的目标是提高对小儿脑肿瘤的理解和治疗。在第一个资助期内，项目负责人共同开发了新型小鼠模型，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，使用这些模型进行新治疗药物的相关临床前测试，并将研究结果转化为临床试验。目前的应用程序扩展了该计划的重点，以涵盖其他儿科脑肿瘤。五个互动项目计划使用人类肿瘤和小鼠模型对大脑中的生长调节进行定向研究，以研究儿科脑肿瘤和大脑发育背景下的信号转导，基因表达和功能。一个行政核心，一个生物信息学和生物技术核心和一个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性肿瘤和新型胶质瘤小鼠模型，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信号的小分子抑制剂的作用机制，他在他的模型系统中显示了消融的髓母细胞瘤。在项目3中，R. Gilbertson将通过对人类肿瘤的分析和小鼠模型的开发来定义髓母细胞瘤的分子亚群，并将描述癌症干细胞及其在髓母细胞瘤亚类中的小生境。在项目4中，P. McKinnon将进一步分析脑肿瘤发展背后的缺陷DNA损伤反应，并将确定DNA修复抑制剂作为脑肿瘤治疗方法的效果。在项目5中，M. Chaisel和C. Sherr将探索成神经管细胞瘤中致癌转化的机制，并将定义调节小脑发育和成神经管细胞瘤中基因表达的microRNAs。该小组内的综合分析将确定儿童脑肿瘤发生中常见和独特的信号转导途径。