Apoptosis is a prevalent and important cell fate during development and homeostasis of multicellular organisms. The long-term goal of our research is to understand the regulation and execution of apoptosis, using the powerful genetic and molecular techniques available in the Drosophila model system. We are particularly interested in how apoptosis is regulated in vivo, and how apoptosis contributes to normal development and homeostasis.

In Drosophila, a cluster of four genes is required for the initiation of apoptosis. This gene cluster serves as an integration point for signaling pathways that regulate developmental apoptosis, and apoptosis in response to cell stress. Each of the genes in the cluster respond to a different array of upstream transcriptional and posttranslational regulators, and the apoptosis of a particular cell is regulated by multiple upstream pathways. We are using genetic and genome wide molecular approaches to examine how specific cells are appropriately selected for death, while their neighbors are unaffected.

The normal death of neural stem cells during development provides us with a tractable model to examine the upstream pathways that regulate cell death. Using a genetic screen, we have identified genetic and epigenetic regulators of neural stem cell death. Our current work is focused on examining how signaling pathways interact with chromatin architecture to activate multiple cell death genes. We are also investigating the developmental consequences of inhibiting neural stem cell death. We expect that these studies will provide important new insight into how the cell death pathway is normally regulated, and how this cell fate can be manipulated in the treatment of disease.