Research

Our laboratory is interested in identifying how cell death signaling pathways can influence inflammation with the hope of identifying novel targets to turn on or off the immune system.

Necrosis is a form of cell death, which involves cell membrane rupture and release of cytoplasmic content into the extracellular milieu triggering an inflammatory response. In turn, unresolved inflammation can lead to further cell death and a persistent state of inflammation, can drive diseases such as cancer, arthritis and cardiovascular disease.

Inhibitors of apoptosis proteins (IAPs), particularly XIAP, are well known for their role in inhibiting apoptosis, whereas the cIAPs, regulate NF-κB and signaling from TNF superfamily receptors. Recent evidence now implicates cIAPs in regulating necrosis versus apoptosis as well as a role in immune signaling. My research now indicates both cIAPs and XIAP regulate cytokine production in vivo in the myeloid lineage, the first physiological role requiring all of these related proteins. Our goal is to understand how IAPs regulate cytokine production and in doing so, determine potential therapeutic targets for resolving chronic inflammation and thus eliminating inflammation as a factor for disease.

Specifically we aim to:

• Determine the molecular role of IAPs in regulating cytokine production and apoptosis versus necroptosis by examining downstream signaling pathways and proteins ubiquitylated by IAPs.
• Understand how IAPs influence myeloid differentiation and function in response to infection and tumour surveillance.
• Determine how chronic inflammation affects chromatin modification and affect predisposition to inflammatory disease.

To do this, we utilize biochemical and molecular techniques combined with genetic knock-­‐out cells and animal models.

For more information see www.thewonglab.com