Research Abstract

The overall goal of our research is to understand the regulation, execution, and role of apoptosis in the context of animal development, using the powerful genetic and molecular techniques available in Drosophila. In our years of research on this topic, my lab has contributed to major insights in the study of apoptosis and generated many of the tools used to examine this process. Our work has extended from the seminal characterization of the cluster of genes required for developmental apoptosis in Drosophila, through biochemical and genetic studies of the how these genes activate apoptosis and how their activity is regulated. These central regulators of Drosophila apoptosis were the first identified IAP inhibitors. The anti-apoptotic IAPs are often upregulated in cancer and contribute to treatment resistance. Chemotherapeutics based on IAP inhibitor proteins are now in clinical trials.

To maximize the impact of our work on the field, we now focus on an important and poorly understood aspect of cell death: how individual cells are selected to die or survive within a tissue. The groundwork for this research is our detailed genetic analysis of neural stem cell apoptosis during development. We have recently characterized how several developmentally important genes collaborate to regulate the death of neural stem cells. Additional transcriptional and epigenetic mechanisms important for neural stem cell death and survival are currently under investigation. We expect our studies to provide important new insight into the regulation of cell death in development and disease.