Investigating the role of candidate immunotherapy target GFRA2 in Ewing Sarcoma
Mentor Name: Sharon Diskin
Using a proteogenomic approach, the Diskin lab has identified GFRA2 as a promising cell surface protein immunotherapeutic target in neuroblastoma and Ewing sarcoma. GFRA2, or GDNF family receptor alpha 2, is a protein found on the surface of certain cells and acts as a receptor for growth factors. The lab has validated surface expression of GFRA2 in neuroblastoma and Ewing sarcoma. They have also demonstrated that GRFA2 silencing results in decreased cell growth in neuroblastoma and discovered an enhancer element driving GFRA2 expression in neuroblastoma cells. We hypothesize that GFRA2 regulates cell growth in Ewing sarcoma and that expression of GFRA2 in Ewing sarcoma is modulated by the EWS-FLI fusion protein as well as an enhancer element. This project will involve both wet-lab and computational studies in Ewing sarcoma. We will 1) silence GFRA2 in Ewing sarcoma cells and assess cell growth, 2) confirm GFRA2 regulation by EWS-FLI by silencing EWS-FLI and evaluating GFRA2 protein expression, and 3) analyze existing epigenomic data to identify putative enhancer elements contributing to GFRA2 expression in Ewing sarcoma.
