Understanding novel mRNA splicing in Ewing Sarcoma
Mentor Name: Jeffrey Toretsky
Our laboratory focuses on Ewing's sarcoma (ES) and the fusion proteins associated with the development and disease progression of ES. Specifically, our team works towards understanding how small molecule inhibitors could be emerging treatment options for ES and other forms of cancer. Small molecule inhibitors are compounds that interfere with target proteins' activity by binding to the proteins and altering their function. In Ewing's sarcoma, oncogenic proteins such as EWS::FLI1 are responsible for altered protein functions. In 2009, our laboratory discovered a small molecule called YK-4-279 that blocked EWS::FLI1. The Toretsky lab discovered that EWS::FLI1 leads to abnormal splicing of mRNA messages that impact ES. The abnormal messages are controlled by specific proteins called splicing regulators. If these proteins can be targeted, it's possible to inhibit their dysregulated role. We will explore manipulating these splicing regulators and determine their specific effects in ES.
