Prof. Dr. Wendy Wei-Lynn Wong

Area of Research

Description of Research Interest

Necroptosis is a programmed form of cell death, involving 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, driving diseases such as cancer, arthritis and cardiovascular disease. Tumor necrosis factor (TNF) is considered to be a master regulator of cytokines and at least three of the top 10 selling drugs block TNF activity. Over time, complications occur with consistent use of anti-TNF drugs. Therefore understanding the signaling networks that occur in normal physiological conditions and in disease states allow us to discover novel therapeutic targets. Inhibitors of apoptosis proteins (IAPs), particularly XIAP, are well known for their role in inhibiting apoptosis, whereas the cIAPs, regulate NF-kB and signaling from TNF superfamily receptors as well as regulating necroptosis versus apoptosis and immune signaling. My research now indicates both cIAPs and XIAP negatively regulate cytokine production in vivo in the myeloid lineage, the first physiological role requiring all of these related proteins. Meanwhile, receptor interacting protein kinases (RIPK) are positive regulators of cytokine production. Our goal is to understand how IAPs and RIPKs regulate cytokine production, cell death or other biological functions such as differentiation or vascular permeability.

Special Expertise

Cell death: necroptosis and apoptosis
TNF signaling
Vascular permeability
Myeloid differentiation

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