Glioma is the most frequent primary tumor in the brain. Its most malignant form, glioblastoma multiforme (GBM) has a very poor prognosis with a median survival of approximately 13 months after diagnosis. As these tumors can resist conventional treatments there is an urgent need for novel therapeutic strategies to combat this devastating disease. The main goal of this project is to develop novel strategies to neutralize glioblastoma stem cells (GSCs). To reach this goal one aim is to resolve how human neural stem cells, exposed to oncogenic stress, activate intrinsic defense mechanisms to prevent malignant transformation. The other aim is to understand how anti-tumorigenic effector programs can be activated in GSCs. Our hypothesis is that the stem cell regulatory TF, SOX21, is necessary for these processes. To achieve these goal we will in part use genome wide analyses (RNA-seq and ChIP-seq) to understand what genes SOX21 binds and regulates in GSCs.