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Ayad Lab

Epigenetic and Kinase Pathway Interactions in Brain Cancers

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Investigator / Contact Person Nagi Ayad

Research

The Ayad laboratory is interested in how epigenetic and kinase pathways interact in the setting of medulloblastoma and glioblastoma. First, we are trying to understand how epigenetic reader proteins are recruited in a specific manner to chromatin. We are studying the epigenetic reader protein Brd4 and we have found that this protein is required for growth of medulloblastoma and glioblastoma tumors. Brd4 inhibition reduces glioma tumor growth. However, how Brd4 does this is not completely understood. We have previously demonstrated that Brd4 controls expression of a long noncoding RNA termed HOTAIR. HOTAIR depletion reduces GBM growth. Interestingly in a recent publication we demonstrate that HOTAIR can be detected in serum from GBM patients. Therefore, HOTAIR can be used as a biomarker for responsiveness of patients to epigenetic pathway inhibitors. 


We are also utilizing big data resources to identify therapeutic combinations for GBM and other brain tumors. We work closely with the LINCS consortium to identify combinations of epigenetic pathway and kinase inhibitors. We have shown that combining kinase inhibitors with bromodomain inhibitors induces synergy in reducing GBM tumor growth. We have also developed a pipeline to identify FDA approved compound combinations for the treatment of GBM.