Remarkably, metazoan development relies on a gene framework which is evolutionarily conserved but is flexible enough to allow evolutionary change. Flies and humans have unexpectedly similar genomes yet they sustain very distinct developments. The fundamental goal of our research effort is to gain insight into the way genes integrate their action to influence differentiation, proliferation, and apoptosis, the fundamental events of development. We are particularly interested in examining the possibility that specific "codes" exist underlying how genes integrate their activities and the degree to which such rules may be valid across tissues and species.
For many years, we have been studying the Notch signaling pathway, one of a few, highly conserved, signaling pathways that control cellular interactions in metazoans. The developmental action of Notch is highly pleiotropic and its action on controlling differentiation, proliferation, and apoptosis in diverse tissues throughout development, depends on how it integrates its activity with other cell signaling mechanisms. An understanding of the molecular rules underlying Notch signal integration impacts not only the definition of Notch biology but also serves as a paradigm to gain general insight into the molecular genetics governing metazoan development. Given the complexity of the issues we are exploring, our experimental approach relies on a diverse, multidisciplinary set of experimental systems and techniques. We are using Drosophila and mice as our main experimental systems to explore the biology and pathobiology of the Notch signaling pathway. We also have a general interest in applying Drosophila genetics as a tool to dissect disease related cellular pathways and have more recently been using this approach to study Spinal Muscular Atrophy.