Grants - V Scholar Grants - Massachusetts - 2015

Miguel Rivera, M.D.

Funded by the Stuart Scott Memorial Cancer Research Fund, with Partial Funding in Year Two From The Ewing Sarcoma Fund

Ewing sarcoma is the second most common bone cancer in children and has a low rate of survival compared to other pediatric cancers.  Genetically, Ewing sarcoma is characterized by a fusion protein known as EWS-FLI1 that is essential for the growth and survival of tumor cells. EWS-FLI1 operates by binding DNA and changing the expression levels of many genes and we believe that studying its mechanisms of action in detail may reveal new opportunities for therapy. We recently analyzed EWS-FLI1 mediated events at thousands of sites across the genome and identified genes that are highly responsive to the fusion protein. Among these genes we found VRK1, a kinase that is involved in coordinating cell proliferation and that represents an attractive therapeutic target. Our experiments show that EWS-FLI1 controls VRK1 expression directly and that Ewing sarcoma cells are highly sensitive to downregulation of VRK1. We now plan to characterize the function of VRK1 in Ewing sarcoma to learn about VRK1 dependent mechanisms in this tumor type and to test the potential of VRK1 and related pathways as therapeutic targets.