Grant: Project Grant

Glioblastoma (GBM) is a common and incurable primary brain tumor that has a 5-year survival rate of less than 10%. GBM tumors are characterized by a high degree of variability in the cells that comprise the tumors, both between and even within individual patients. Thus, within a patient's tumor there are cells that have different cancer-causing mutations, and cells that have different phenotypes (such as the genes they express, how invasive they are and how they respond to different drugs) that we term "cell states". Furthermore, there is a growing body of evidence that cells can switch between different states as tumors progress and undergo treatment. This variability and plasticity is a major contributor to the failure of many drugs that have been tested for treatment of GBM-drugs may target only a subset of cell states, or cells with "switch" states to evade treatment. Our research is focused on identifying the genes involved in establishing different cell states in GBM and conferring the ability of cells to switch between states. We will use CRISPR based genome-editing technologies to systematically screen every gene in the human genome to uncover the genes controlling these processes. After genes are identified in our screen, we will perform additional experiments to confirm their roles in GBM samples from multiple patients and understand how these genes function in GBM. The knowledge gained from these screens can be used to better understand how tumors evade therapies and inform on new strategies that would seek to limit the capacity of cells to switch between states.