Genome-wide RNA-seq screen for KANSL2-dependent genes that influence the cell state (or cell identity) under Ionizing Radiation treatment
University of Colorado
Glioblastoma is the most common and aggressive tumor of the central nervous system. Current treatment involves a combination of surgical removal and ionizing radiation (IR). Unfortunately patient survival averages 12-18 months due to recurrence. This recurrence is due to the existence of a subpopulation, called glioma stem cells (GSC), with an enhanced capacity for repairing DNA damage. It has been shown that IR treatment upregulates the stemness transcriptional network, further contributing to the development of tumor resistance to treatment. Our lab is characterizing KANSL2, a novel protein involved in the stemness network of glioblastoma and a critical player during tumor development. Its expression is enriched in GBM tumors, particularly in the perivascular niche where stem cells reside. KANSL2 is a subunit of the epigenetic NSL complex, whose acetyltransferase MOF has been reported to be necessary for the activation of the ATM DNA repair pathway following IR. Our aim is to determine target genes within the KANSL2 transcriptional network that contribute to the regulation of the cell plasticity under IR treatment. Understanding the molecular mechanisms of GSC resistance to IR is critical for the development of more effective therapeutic approaches for treating glioblastoma.