While apoptosis is the best-known form of programmed cell death, recent work has demonstrated the existence of another form of cell death called "programmed necrosis." Apoptosis leads to cellular shrinkage, packaging of dead cell contents, and rapid phagocytosis; programmed necrosis involves cellular rupture and release of inflammatory signaling molecules. For this reason, apoptosis is non-inflammatory when it occurs in vivo, while programmed necrosis is thought to trigger potent inflammation and immune responses. Interestingly, the same signaling events can trigger either form of cell death; signals such as TNF or TLR stimulation can lead to cellular survival, apoptosis or programmed necrosis depending on the cellular context in which they occur. This "decision" is critical, because of the drastically different immune outcomes associated with apoptosis and programmed necrosis.
The Oberst lab focuses on understanding how pleiotropic signals lead to cellular survival, apoptosis, or programmed necrosis, and how each outcome influences immune responses. We use cell biology and biochemistry techniques to study how apoptosis and programmed necrosis are initiated, and to create systems in which each form of cell death can be specifically triggered. We then use these tools to study the effect of each type of cell death in vivo, with the goal of understanding their role in processes such as inflammation, autoimmunity, tumor suppression, and immune responses to pathogen infection.
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Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research