(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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S (J1))
Program Officer
Mietz, Judy
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
St. Jude Children's Research Hospital
United States
Zip Code
Zhan, Hong; Aizawa, Kenichi; Sun, Junqing et al. (2016) Ataxia telangiectasia mutated in cardiac fibroblasts regulates doxorubicin-induced cardiotoxicity. Cardiovasc Res 110:85-95
Grigaravicius, P; Kaminska, E; Hübner, C A et al. (2016) Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain. Cell Death Differ 23:454-68
Qaddoumi, Ibrahim; Orisme, Wilda; Wen, Ji et al. (2016) Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Acta Neuropathol 131:833-45
Sturm, Dominik; Orr, Brent A; Toprak, Umut H et al. (2016) New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell 164:1060-72
Baker, Suzanne J; Ellison, David W; Gutmann, David H (2016) Pediatric gliomas as neurodevelopmental disorders. Glia 64:879-95
Phoenix, Timothy N; Patmore, Deanna M; Boop, Scott et al. (2016) Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell 29:508-22
Zhai, Yali; Kuick, Rork; Tipton, Courtney et al. (2016) Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. J Pathol 238:21-30
Zhu, Liqin; Finkelstein, David; Gao, Culian et al. (2016) Multi-organ Mapping of Cancer Risk. Cell 166:1132-1146.e7
Patel, Yogesh T; Jacus, Megan O; Davis, Abigail D et al. (2016) Simvastatin Hydroxy Acid Fails to Attain Sufficient Central Nervous System Tumor Exposure to Achieve a Cytotoxic Effect: Results of a Preclinical Cerebral Microdialysis Study. Drug Metab Dispos 44:591-4
Morfouace, Marie; Nimmervoll, Birgit; Boulos, Nidal et al. (2016) Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors. J Neurooncol 126:225-34

Showing the most recent 10 out of 168 publications