Aberrations in the regulatory network controlling fate choice decisions of stem/progenitor cells during development have been the leading cause of brain tumors and many other cancers. Recent studies have discovered a highly tumorigenic subpopulation of cells that reside within the tumor mass with stem/progenitor-like properties. Although these cells represent only a small percentage of glioma cells, they tend to be resistant to therapy and have the ability to self-renew. One of the current approaches for targeted therapies is to identify and drug critical factors and/or pathways specifically expressed in the glioma stem cells. The stem/progenitor-like cells found in glioma tissues express several developmentally important transcription factors. One such factor is Olig2, a central nervous system-specific factor important for gliogenesis and for the formation of certain subtypes of neurons. We have recently shown that Olig2 is critical for glioma formation in patient-derived xenograft models. Importantly, we found that targeting Olig2 can radiosensitize human glioma cells in a p53-dependent manner. Current efforts in Mehta laboratory are focused on 1) investigating the mechanisms involved in normal CNS development that have been pilfered by glioma cells and 2) identifying factors which would be critical for glioma growth and their resistance to therapy.