Funded Research
August 15, 2008: The Liddy Shriver Sarcoma Initiative is funding a 2-year, $100,000 research study: Analysis of NR0B1 in Ewing’s sarcoma. The funding of this grant is made possible by a generous gift from the Arlo and Susan Ellison family and by a generous gift from Truus van der Spek, in loving memory of her son Paul Onvlee.
This study is led by Stephen L. Lessnick, MD, PhD at Huntsman Cancer Institute at the University of Utah. Dr. Lessnick told us:
"Ewing’s sarcoma is a highly aggressive bone-associated tumor that is primarily diagnosed in adolescents and young adults. Most cases of Ewing’s sarcoma express a unique fusion oncoprotein, EWS/FLI. EWS/FLI functions as a transcription factor to dysregulate genes involved in cancer development. We recently developed a system to study EWS/FLI in its native cellular context, that is, in Ewing’s sarcoma itself. By “knocking-down” endogenous EWS/FLI expression in patient-derived Ewing’s sarcoma cell lines, we defined the full complement of EWS/FLI gene targets. Following an RNAi-based screening approach, we identified NR0B1 as a key mediator of the transformed phenotype of Ewing’s sarcoma cells. We now propose a series of studies designed to determine the molecular mechanisms of NR0B1 function in Ewing’s sarcoma. We have already defined regions of NR0B1 that are required for oncogenic transformation. We will complete the mapping of these regions, and determine whether these domains are involved in the protein-protein interactions we have defined for NR0B1. We will also determine the role of these NR0B1-interacting proteins on Ewing’s sarcoma transformation. These data will allow us to understand the molecular mechanisms by which NR0B1 participates in Ewing’s sarcoma development. This is important as we strive to understand the pathways involved in Ewing’s sarcoma development, and use this knowledge to identify new therapeutic approaches for this devastating disease."
You can read more about the approach Dr. Lessnick is taking in this study in his article, "EWS/FLI and its targets in Ewing’s sarcoma: a progress report and future directions," which appears in the August 2008 issue of ESUN.
Editor's Update: Huntsman Cancer Institute released a news story about this study on August 31, 2009. This grant was credited in the Journal of Clinical Investigation article entitled, "CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis." The Initiative has also funded previous research on EWS/FLI at Huntsman Cancer Institute.