Novel relationships of splicing factors in temozolomide-resistant glioblastoma

Drug resistance happens rapidly in the devasting brain cancer glioblastoma (GBM). GBM has limited therapeutic options with few advances being made in the past decade. Better understanding resistance to the standard o care chemotherapeutic agents, temozolomide, through RNA binding proteins (RBPs) and RNA processing will be the goal of my K00 research. I will transition from Georgetown University to Northwestern in order to pursue my independent GBM-focused research with Dr. Shi-Yuan Cheng. My post-doctoral research will investigate the role a rewired DNA damage response plays in RNA binding protein aggregation. Furthermore, aggregating RBPs have been previously shown to change the RNA transcript landscape through both alternative splicing changes and mRNA sequestering. The use of proteomics, a large cohort of patient samples, and the Cheng Lab’s expertise in RNA biology will allow me to successfully investigate RBP aggregation both mechanistically and biologically. Upon completion, this project will give better insight into the role RBPs and RNA processing play in GBM drug resistance. Such information will hopefully lead to better targeted therapies down the road but may also assist in our overall understanding of aggregating RBPs in other central nervous system disorders. Looking to the future, these studies will lay the groundwork for a basic understanding of RBPs and RNA biology in GBM that I can continue to investigate throughout my academic career.