Genetic networks in development and cancer

The broad objective of my laboratory is to identify genes that are crucial for embryonic development, and when mis-regulated results in cancer. Within this framework we study the function and regulation of transcriptional co-regulators, (co-factors), that serve as molecular “hubs” connecting signaling to transcription and mediate pathways crosstalk. Of interest are co-factors that possess defined enzymatic activities, and therefore have the potential to serve as targets for early detection and intervention. Our aims are to dissect the upstream signaling pathways that regulate co-factors function, and to identify cis-acting factors, direct targets, as well as negative regulators of transcriptional co-factors during development and oncogenesis. Toward these aims we use Drosophila as a model organism combining genetics, and genomics tools (chromatin–profiling DamID, expression arrays), as well as mammalian cell biology. One advantage of this approach is that we can rapidly translate and evaluate the relevance of findings from the Drosophila system to human cancer cells.
We currently focus on the role of the Myc oncogene and a group of novel transcriptional co-factors during early embryonic development. In humans, Myc is required for cell growth, proliferation, apoptosis, as well as reprogramming of somatic cells into stem cells. Mis-regulation of Myc results in leukemia lymphomas and neuroectodermal tumors. In Drosophila, in addition to its classical function as a regulator of cell growth, we found that dMyc is required for promoting neuronal fate and mitosis of neuroblasts. Myc’s function in neuroblasts is part of an emerging novel multi-gene network that includes several novel co-regulators. The function and regulation of this emerging network is the center of our work.