Affiliations
|
Professor,
Pediatrics,
Pediatric Hematology/Oncology
|
Research Director,
Pediatric Hematology/Oncology
|
Leader,
Center for Translational Technologies
|
Member,
CTSI,
California NanoSystems Institute,
Child Health Research,
Pediatric Bone and Soft Tissue Sarcoma Program
|
Research Interests
Genomic mutation is 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. My lab has focused 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. We have isolated this chimeric molecule both as genomic and cDNA clones, and have 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 lead us 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.
Publications
Error in include template "/web/fdb5/www/gpb/institution/publications": can't read "allow_redirect_p": no such variable