Normal and Neoplastic Growth Regulation in the Brain

这个项目的目标是增加对发育中的大脑正常和肿瘤生长的分子基础的理解。最终目的是利用这些知识来设计治疗髓母细胞瘤的新策略，髓母细胞瘤是最常见的小儿中枢神经系统恶性肿瘤。这一目标正在通过四个互动项目来实现，这些项目由一个行政核心和一个生物信息学和微阵列核心支持，研究不同信号通路在中枢神经系统和脑肿瘤生长中的作用。在Project 1中，T. Curran利用成神经管细胞瘤小鼠模型来研究Shh/Ptc/Smo通路在肿瘤发生中的作用。这涉及到在细胞培养和体内使用药理学抑制剂，对吉尔分子特性进行表征和比较

The goal of this program project is to increase understanding of the molecular basis of normal and neoplastic growth in the developing brain. The ultimate objective is to use this knowledge to devise novel strategies for treatment of medulloblastoma, the most common pediatric malignancy of the central nervous system. This objective is being pursued through four interactive projects that investigate the role of different signaling pathways in the growth of the central nervous system and brain tumors supported by an Administrative Core and a Bioinformatics and Microarray Core. In Project 1, T. Curran utilizes a mouse model of medulloblastoma to investigate the role of the Shh/Ptc/Smo pathway in tumorigenesis. This involves the use of pharmacological inhibitors in cell culture and in vivo, a molecular characterization of Gill and comparison of the epigenetic and genetic alterations underlying medulloblastoma by nuclear transplant into oocytes. In Project 2, P. McKinnon investigates the contribution of DNA damage signaling to medulloblastoma formation. This project is based on the characterization of a novel model for medulloblastoma in mice lacking DNA Ligase IV and p53. This analysis will involve comparison of gene expression microarray profiles of the different medullobalstomas in the program. In Project 3, R. Gilbertson is investigating the role of ERBB2 in human medulloblastoma. This involves the characterization of human medulloblastoma cell lines using pharmacological and gene expression microarray approaches. The information will be compared to the data obtained on mouse models and an existing database of human brain tumors. A mouse model will be created in which ERBB2 is expressed in cerebellar granule neurons. In Project 4, S. Baker is studying the role of the Pten signaling pathway in growth regulation in the brain. This includes characterization of the function of downstream effector genes in the cerebellum and the creation of new mutant mouse strains to investigate its contribution to growth, proliferation and tumorigenesis.