Research in my lab investigates proteins that can regulate both inflammation and cell death. We are revealing how these proteins contribute to inflammatory diseases including: psoriasis, rheumatoid arthritis, Crohn’s disease, as well as cancer.
Our goal is to translate our discoveries into new treatments for these scourges.
We are taking several approaches to explore the best way that IAP antagonists can be used in the clinic to treat cancer. This is an area of intense research world-wide but we have unique advantages including:
Using these reagents we are looking for the cancer types most responsive to birinapant killing and novel drug combinations that can overcome the resistance of other cancer types.
Team members: Dr Gabriela Brumatti, Dr Najoua Lalaoui
Using laboratory models of psoriasis and systemic inflammation we have shown that genetic loss of the key necroptosis effectors RIPK3 and MLKL significantly attenuates many aspects of the disease.
Working with other divisions at the institute, we have discovered novel small molecular inhibitors of necroptosis which we are now testing in this and other disease models.
Team member: Dr Joanne Hildebrand
We have shown that IAPs and RIPK2 play an important role in regulating signalling from NOD receptors, essential intracellular receptors that detect and respond to bacterial products. We are exploring a small molecule approach to explore this pathway and with collaborators at the institute we have developed and characterised a new RIPK2 inhibitor.
This has a fascinating mode of action: it delays signalling events such as NF-κB activation by only an hour or less, but completely inhibits the production of inflammatory cytokines by this pathway. We are exploring this further with mass spectrometry approaches.
Team member: Dr Ueli Nachbur
cIAPs and RIPK1 play important roles in regulating the signalling outcome downstream of TNF/TNFR1 activation. We have a long-standing interest in understanding how they function in this role, using a combination of genetics, small molecule inhibitor and mass spectrometry approaches.
More recently we have expanded our purview of this fascinating signalling paradigm by exploring the role of other regulators of this pathway including the linear ubiquitin assembly complex comprising the proteins SHARPIN, HOIL-1 and HOIP.
We collaborate with many research groups at WEHI that have overlapping interests.