The human body is estimated to remove more than 200 billion dead cells every day. This clearance of apoptotic cells, or efferocytosis, is carried out by phagocytes such as macrophages, which are fewer in number. Efferocytosis is essential for normal development and tissue homeostasis, but also pathogen defense and anti-tumor immunity. A single phagocyte typically ingests an entire apoptotic corpse, essentially doubling its content. Because phagocytes often ingest multiple targets in succession, we propose the existence of “rapid-response circuits” composed of kinases that sense and activate in response to the change in a given solute, and solute transporters downstream of these kinases that impart the necessary flux of solutes. We believe these circuits allow phagocytes to handle the risk that corpse content poses to the homeostasis of both the phagocyte and ultimately the host. The central focus of our research program is to understand these rapid-response circuits governing how a phagocyte manages such excess cargo influx, how this relates to host immune function and homeostasis, and how these processes are exploited in cancer development and progression.
The Perry lab combines cell biological, immunological, and informatics approaches to investigate the following: