Ewing sarcomas are highly aggressive tumors that primarily affect children and young adults. They are believed to arise from neural crest stem cells - rare cells that contribute to the formation of multiple tissues throughout the body. Ewing sarcomas contain an abnormal gene called EWS-FLI1. The precise way in which expression of EWS-FLI1 causes Ewing sarcoma remains to be determined, but it is known to involve disruption of normal gene expression. Lawlor believes that this disruption is due, at least in part, to changes in some of the epigenetic marks on the DNA (DNA methylation) that result in turning on the expression of genes that should be off and turning off the expression of genes that should be on. This project will use an innovative model to generate neural crest stem cells in the laboratory. Lawlor will study the ways in which expression of EWS-FLI1 affects the epigenetic marks in these neural crest stem cells and how EWS-FLI1 initiates tumor formation. She will also determine whether the epigenetic alterations in Ewing sarcoma cells can be corrected by treatment with a new targeted drug that prevents DNA methylation. These studies will provide novel insights into normal neural crest cell biology and could facilitate the development of more effective, less toxic therapies, such as DNA methylation inhibitors, to specifically target this pediatric malignancy.
Elizabeth R. Lawlor, M.D., Ph.D., physician-scientist at the Childrens Hospital Los Angeles, Saban Research Institute; assistant professor in the Departments of Pediatrics and Pathology at the University of Southern California, Keck School of Medicine
Watch an interview with Elizabeth R. Lawlor, M.D., Ph.D.
Updated: Mar 29, 2010