Dr. Christopher Denny's research focuses on genomic mutation as a primary force in the genesis of human malignancy. Molecular isolation of genes involved in tumor-specific rearrangements has identified mechanisms of tumorigenesis and has formed a basis for studying transformation pathways of human cancers.

Denny's lab has focused specifically on the 11:22 translocation that occurs in Ewing's sarcoma and PNET, two lethal and poorly understood pediatric cancers of presumed neural crest origin. This rearrangement fuses a previously unknown gene, termed EWS, to FLI-1, a member of the ETS family of transcription factors. Denny's lab has isolated this chimeric molecule both as genomic and cDNA clones, and has shown that EWS/FLI can transform rodent fibroblast lines. This is consistent with the notion that it plays an active role in Ewing's sarcoma oncogenesis.

Mutation analyses, DNA-binding studies, and subcellular localization experiments have led Denny and his colleagues to hypothesize that EWS/FLI is acting as an aberrant transcription factor that is qualitatively different from normal FLI-1. A novel method for identifying differentially expressed genes has been developed to isolate potential target genes that are modulated by EWS/FLI. This cohort of EWS/FLI regulated genes is now being analyzed with a long-term goal of defining important genetic pathways that are activated during cellular transformation.