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Mechanisms of OTX2 Mediated Chromatin Regulation in Medulloblastoma

Massachusetts General Hospital
Miguel Rivera, MD
Grant Type: 
Innovation Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Medulloblastoma is the most common pediatric brain cancer and is divided into four subgroups with different molecular features and outcomes. There is a pressing need to develop new therapies for these tumors, particularly for Group 3 patients who have the lowest five-year survival.  We have recently found that the transcription factor OTX2 is a major regulator of gene activation in Group 3 medulloblastoma and controls many critical genes in this disease. OTX2 operates primarily by binding regulatory DNA elements known as enhancers but its mechanisms of action at these sites are not well understood. 

Project Goal
We now aim to understand these mechanisms by identifying proteins that cooperate with OTX2 and by determining which OTX2 target genes are important for cell growth and survival. We believe that these studies have great potential to reveal genes and pathways that may serve as therapeutic targets for medulloblastoma.