Drosophila as a model system to understand Wnt signal transduction and epidermal cell patterning.
My laboratory explores the molecular mechanisms of pattern formation in developing embryos. We focus on the Wingless(Wg)/Wnt class of secreted growth factor: these molecules promote cell-cell communication leading to important cell fate decisions during the development of both vertebrate and invertebrate embryos. In addition, this highly conserved pathway is essential for maintaining stem cell populations and is associated with human cancers when inappropriately activated in adult tissues. Wg/Wnt molecules have proven difficult to work with biochemically because they associate tightly with cell membranes. Therefore, we exploit the powerful genetic and molecular techniques available in Drosophila to approach basic questions about Wg/Wnt signal transduction. Current work in the lab includes analysis of genes discovered as suppressors or enhancers of wg mutant phenotypes, which may identify new control mechanisms for the pathway. In earlier work, we found that the Wg-activated transcription factor, dTCF, can act as either a repressor or an activator of Wg target genes, and our screens have uncovered other factors that may influence this genetic switch. We have also characterized a Drosophila homolog of the human tumor suppressor, APC, which negatively regulates the Wg/Wnt signaling pathway, and we are currently studying other genes that show similar properties. We use cultured human cells to determine whether gene activities we have discovered and characterized in the fly embryo are relevant to the mammalian Wnt pathway as well.