My lab is interested in exploring therapeutic strategies that target tumor self-renewal and regeneration in glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor. A subset of tumor cells known as cancer stem cells often leave brain tumors with the capacity to regenerate after initial treatment. However, the factors that control this regeneration and resistance to current therapies are unknown, leaving their growth difficult to block. We aim to understand how the nuclear hormone receptor and transcription factor TLX is implicated in the maintenance of GBM stem cell growth and resistance to therapeutics. Elevated levels of TLX are present in the more aggressive forms of GBM and can repress cellular mechanisms that normally block tumor formation. To tease out the role of TLX in GBM stem cells, we will apply chemical genetic and next-generation genomic approaches to understand how TLX controls the genes required to maintain self-renewal. We will engineer systems that can quickly perturb TLX levels in cells and in a lab-grown GBM tumor model called an organoid. Finally, we hope to use chemical probes to promote the degradation of TLX in order to annihilate its ability to activate tumor survival genes. By profiling changes in gene expression and in the chromatin landscape of GBM during TLX perturbation, we hope to provide a precise map of TLX-controlled genes in GBM stem cells, and insights toward new targets for a debilitating cancer, for which there is no effective treatment.