Cross-talk between cell death and inflammatory signalling pathways

Cross-talk between cell death and inflammatory signalling pathways

Project details

Inhibitor of APoptosis (IAP) proteins repress programmed cell death. As such, chemical IAP antagonists have been developed as cancer therapeutics, and have also been indicated for treating infectious diseases.

We recently revealed how IAP loss can also trigger inflammasome-mediated pro-inflammatory cytokine activation. Consistent with this, IAP mutations in people can result in systemic inflammatory disease. However, the physiological regulation of IAPs, and its impact on inflammasome activity, remain poorly defined. 

This project will use genetic and biochemical approaches to identify the signalling pathways that control IAP activity, and examine how these impact inflammasome driven innate-immunity. This will provide new strategies for targeting cell death machinery in inflammatory and infectious diseases.


About our research group 

We have a strong interest in studying how the signaling pathways leading to cell death can also trigger immune responses through the activation of pro-inflammatory cytokines (Khan et al., Curr. Opin. Imm. 2014).

Our recent studies have investigated the role of mitochondrial apoptosis (Allam et al., EMBO Reports 2014), death receptor apoptosis (Vince et al., Immunity 2012) and RIPK3-MLKL mediated necroptosis (Lawlor et al., Nature Comm. 2015) on inflammasome activation. These have revealed new paradigms for how the cell death machinery, such as IAPs, can directly influence inflammatory responses.

Our ongoing studies are examining if these mechanistic insights are relevant to the pathogenesis of inflammatory driven diseases such as arthritis, diabetes and microbial infection.


Kate Lawlor in the lab
Inflammation division

Dr James Vince

Dr James Vince in a laboratory
Laboratory Head

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