Mechanisms Regulating Medulloblastoma Progression
Our long-term goal is to design better therapies for the treatment of pediatric brain tumors. Medulloblastoma, a pediatric malignancy of the cerebellum, has the highest incidence rate of all malignant pediatric brain tumors and remains largely incurable despite the use of aggressive therapies with strong side effects. In addition, although metastasis or leptomeningeal dissemination of tumor cells is a major challenge in medulloblastoma treatment, the mechanisms underlying this process are poorly understood. Thus, novel targets for clinical intervention are urgently needed to increase survival rates and reduce side effects.
We will focus our study on a novel protein that plays a critical role in brain development. Our proposal will test the hypothesis that loss or reduction of this protein is critical for medulloblastoma development and metastasis. Experiments will establish a novel and unique mouse model of medulloblastoma metastasis that will be considerably useful for understanding the mechanisms regulating medulloblastoma dissemination and for testing novel therapies targeting metastasis. In addition, experiments in Aim2 will identify novel regulators of leptomeningeal dissemination of medulloblastoma cells and thus will shed light on the molecular mechanisms used in medulloblastoma metastasis. These novel regulators will be then investigated further for their role in pediatric brain tumor progression and their potential use as therapeutic targets.