The unifying theme encompassing the work in our lab is to understand how growth and patterning are regulated. Three areas of interest are:
The morphogen Decapentaplegic (Dpp) provides an ideal entry point to delineate an intrinsic growth and patterning program down to its molecular basis. We have continually refined our understanding by applying state of the art technologies to rigorously interrogate the role of Dpp in growth.
Cell competition is a process by which otherwise viable cells are actively eliminated due to the presence of more competitive cells. It is a conserved phenomenon and occurs in various developmental and experimental contexts. Competitive elimination represents a safeguard mechanism that potentiates animal development. The elucidation of the interplay between loser and winner cells in the process of cell competition could provide new therapeutic targets diseases such as cancer.
An important step forward was our discovery that in components of the evolutionarily ancient and conserved innate immune system are used to eliminate “unfit” Drosophila cells. Another was the discovery that Xrp1 is a transcription factor required for cell competition-driven elimination of loser cells.
We are continuing to refine our understanding of cell competition and working to integrate these insights into a holistic model of cell competition and tissue fitness.
The Toll pathway is central to the innate immune response to Gram positive bacteria, fungi, viruses and cancer cells both in Drosophila and in mammals. The pathway is also important for the elimination of loser cells in cell competition. Recently, we found that the Toll pathway is at the nexus of the trade-off between innate immunity and growth during development.
We are continuing to explore this novel aspect of Toll signaling.