The goal of the lab is to understand the molecular events that lead to the development of cancer in children. We have focused our efforts on Ewing's sarcoma, a tumor with a peak incidence in the teenage years. Ewing's is most often found as a bone associated tumor, but it can also occur in the soft tissues. Microscopically, Ewing's sarcoma often appears as sheets of small, round, blue cells. It is uncertain what the cell of origin of Ewing's sarcoma is, and this continues to be a source of much speculation.
On the molecular level, Ewing's sarcoma is characterized by a recurrent chromosomal translocation, the t(11;22)(q24;q12), that generates a fusion between the EWSR1 and FLI1 genes. The EWS/FLI fusion protein functions as an aberrant transcription factor to dysregulate genes involved in the formation of Ewing's sarcoma.
We are interested in asking (1) what genes are dysregulated by EWS/FLI, (2) what are the roles of these genes in the transformation process, and (3) what other genetic alterations are required for the genesis of Ewing's sarcoma?
To address these questions, we are taking a number of approaches. We have developed model systems for the study of EWS/FLI. These systems allow us to turn EWS/FLI on and off at will. We have analyzed these model systems on oligonucleotide microarrays to determine which genes are altered following EWS/FLI expression. As we develop hypotheses regarding EWS/FLI-regulated genes, we turn back to the bench to functionally validate these targets, and to understand their roles in the development of Ewing's sarcoma.
In some instances, we've identified genes that are likely to actively contribute to the oncogenic potential of the tumor. In other instances, we've identified genes that are likely to contribute to the phenotype of the tumor. In still other cases, we've identified tumor suppressor pathways that must be bypassed in the process of tumorigenesis.
Our ultimate goal is to combine all of the approaches from the lab to develop a complete understanding of Ewing's sarcoma, and to apply this understanding to the clinic. In this way, we hope to positively impact the treatment of children with cancer.