As we develop, we make too many cells. These extraneous cells are eliminated by an orderly processes of cell death (apoptosis) and cell engulfment (efferocytosis) to ensure proper development. These processes are also important in adults for maintaining a proper homeostatic balance in the body. Errors in these signaling pathways can result in the progression of cancer and auto-immune diseases. My research investigates the molecular mechanisms that ensure the proper elimination of effete and dying cells. In particular, we are interested in the link between apoptosis and efferocytosis – how do cells that are triggered to die signal that they need to be eliminated by phagocytosis? While some of these cues have been discovered, our understanding of this process if far from complete. To this end we are using a novel, genetically-encoded, cell engulfment reporter to identify the genes required for the proper phagocytosis of apoptotic cells. We use the fruitfly Drosophila melanogaster as our model system for these studies on account of its high degree of conservation of gene function with humans, the large array of molecular-genetic, biochemical, and imaging tools available in vivo and in vitro, and the ability to easily observe developmental phenomenon in the living, intact animal.
Hsp27 phosphorylation, oligomerization, localization, structure, and function
In a related project, we have also been investigating the molecular mechanisms of Hsp27, which is a ubiquitous small heat shock protein that is conserved across species. Hsp27 can function in an anti-apoptotic capacity that spares doomed cells from being eliminated and thus contributing to the disease state, though its precise mechanism of action is muddied by its complex regulation via changes in expression, localization, phosphorylation, and oligomerization. We have undertaken computational and experimental studies to better understand how this key, multifunctional protein is regulated in response to stress and other cellular insults.