Thursday, December 26, 2024
12/26/2024
The long-term goal of the proposed research is to understand how early aberrant events in cerebellar development lead to pediatric brain tumor. Pediatric cancer is the leading cause of disease-related death in children, and solid tumors of the central nervous system account for approximately 20% of all pediatric cancers. One type of solid tumor is medulloblastoma, a highly invasive tumor that arises from the developing cerebellum; these tumors account for an estimated 8000 cases per year worldwide. While 70% of diagnosed children survive over five years, current treatments severely compromise quality of life. Therefore, learning more about disease-specific genetics and etiology will guide individualized treatment, increase remission rates, and reduce long-term toxicity. This proposal seeks to validate a recently identified medulloblastoma hereditary predisposition gene and elucidate its function. To thoroughly investigate the mechanism of action, this F32 proposal combines critical training in mouse biology with cell biology and human tumor analysis to address the following specific aims: 1) investigate the function of a frequently mutated hereditary predisposition gene in normal cerebellar development and in tumorigenesis, 2) determine how loss of this gene affects tumor formation and progression in tumor-susceptible cells, and 3) validate these findings in human patient-derived orthotopic xenograft tumor models. These studies have the potential to determine how the most frequent germline mutated gene functions to drive tumorigenesis. These results will be essential for appropriate genetic counseling of patients with this mutation and their families, and they will provide a solid foundation for preclinical testing and treatment of these tumors.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).