Centre for Functional Genomics and Human Disease

Cytokine Signaling in Disease

The interleukin-6 cytokine family plays an important role in maintaining homeostasis of various biological systems, including haemopoiesis, immunity and bone metabolism. All members of the interleukin-6 cytokine family use a cell surface receptor called gp130 to transmit intracellular signals controlling cellular functions such as proliferation, differentiation, maturation, and survival.

Although it has been well established that gp130 activates multiple signalling pathways, such as STAT1, STAT3 and SHP2/ERK MAPK, it remains unclear which gp130-dependent signalling pathways are required for the physiological actions of this cytokine family during homeostasis. To address this, we are using in vivo models in which specific mutations in gp130 disrupt the normal activation of certain gp130-dependent signalling pathways. Using this approach, we have demonstrated the broad pathological consequences of uncontrolled gp130-dependent signal transduction from this cytokine family, resulting in blood disorders, chronic inflammatory responses, lung disease and stomach cancer.

The projects undertaken in our group encompass numerous molecular biological and genetic approaches to better understand the mechanisms by which uncontrolled signal transduction from this cytokine family leads to these disease states. This research will ultimately assist in identifying genes which can potentially be used as biomarkers for disease and also targets for the design of therapeutic strategies.