Under the leadership of Dr. Miguel Rivera at Massachusetts General Hospital, this project focuses on medulloblastoma. Medulloblastoma is the most common malignant brain cancer in children and consists of at least 4 different subgroups that differ in prognosis (Wnt, SHH, Group 3 and Group 4) (2-6). The most well characterized subtypes are driven by abnormalities in well-known developmental pathways (Wnt and SHH) whereas the mechanism responsible for Group 3 and 4 tumors are not fully understood (5-8). Current treatment regimens for medulloblastoma involve a combination of surgery, radiation and chemotherapy but toxicity and high rates of recurrence continue to be significant clinical problems. There is thus a pressing need to develop new treatment strategies for medulloblastoma, particularly for Group 3 tumors which comprise 30% of medulloblastoma cases and have the poorest prognosis (1).  This project has 3 aims: to determine the 3D chromosome conformation of medulloblastoma genomes; to test the function of critical enhancers and their target genes in Group 3 medulloblastoma and to identify chromatin regulators with critical roles in medulloblastoma.