William May

Associate Professor

Pediatrics
The Saban Research Institute
Childrens Hospital Los Angeles

Research Topics

  • Cancer Genetics,
  • Cancer Cell Biology,
  • Gene Regulation/Transcription

Research Overview

Title: The role of EWS/ets chimeric proteins in the biology of the Ewing Sarcoma Family of Tumors.

A diverse collection of human malignancies are associated with aberrant transcription factors. The Ewings Sarcoma Family of Tumors (ESFT) are a common bone and soft tissue tumor of adolescence and young adulthood, including more traditional diagnosic entities such as peripheral Primitive Neuroectodermal Tumor (pPNET) and Askin Tumor. Relentlessly aggressive, the members of this tumor family are highly undifferentiated and offer few clues as to their origins. However, one feature nearly all these tumors share is the presence of an aberrant transcription factor fusing the N-terminal portion of the EWS gene to the C-terminal portion of an ets transcription factor. This striking association and multiple lines of experimental evidence indicate that the biology of these chimeric transcription factors is central to the development and sustenance of these tumors. Therefore, a major objective in understanding the biology of these unique tumors is to elucidate those targets of biologic consequence which are aberrantly regulated as a result of EWS/ets chimera.

The focus of my lab effort is to accomplish this goal though the use of an expression cloning approach in which biologically relevant genes that act downstream of EWS/FLI are isolated, identified, and evaluated for their role in tumor biology. Using shuttle vector systems, we have identified targets of EWS/ets transcriptional deregulation such as Platelet Derived Growth Factor C (PDGF-C) which appear to in part mediate the oncogenic effects of EWS/ets proteins. Using these techniques and our knowledge of already identified targets, we can begin to trace some of the steps that result in the development of these malignancies. This understanding will provide a valuable paradigm for the study of the wide array of malignancies that are associated with aberrant transcription factors.