Cancer and Immune Signalling

Cancer and Immune Signalling Research Group

Research Group Head

ciiid-image2The projects undertaken in this group combine molecular biological and genetic approaches, together with human translational studies, to identify the mechanisms by which uncontrolled signal transduction from the interleukin (IL)-6 cytokine family, pattern recognition receptors (such as toll-like receptors) and inflammasomes lead to inflammation-associated cancers (stomach, lung, pancreatic) and emphysema/chronic obstructive pulmonary disease (COPD).

The IL-6 cytokine family plays an important role in maintaining homeostasis of various biological systems, including pulmonary function, the gastrointestinal tract, and immune/inflammatory responses. Furthermore, the deregulated over-production of IL-6 family cytokines is implicated in many human cancers, (stomach, lung, pancreatic, colon), inflammatory diseases (arthritis, inflammatory bowel disease), and emphysema/COPD. To identify how IL-6 family cytokines promote disease pathogenesis, Professor Jenkins’ team uses in vivo pre-clinical disease models in which specific signalling pathways downstream of IL-6 family cytokines are over-activated. Using this approach, they have demonstrated the broad pathological consequences of uncontrolled activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 pathway. While these studies demonstrate that STAT3 activated by specific members of this cytokine family promote cancer and chronic inflammatory responses, they have also uncovered that under certain situations the JAK/STAT3 pathway cross-talks with toll-like receptors and other pattern recognition receptors (including those linked to inflammasome activation) to drive disease.

Research Projects

Research Group

Selected publications

  • Greenhill, C.J., Rose-John, S., Lissilaa, R., Ferlin, W., Ernst, M.,Hertzog, P.J., Mansell, A., JENKINS, B.J. (2011) IL-6 Trans-Signaling Modulates TLR4-Dependent Inflammatory Responses via STAT3. J. Immunol. 186:1199-1208.

  • Ruwanpura, S.M., McLeod, L., Miller, A., Jones, J., Bozinovski, S., Vlahos, R., Ernst, M., Armes, J., Bardin, P.G., Anderson, G.P., JENKINS, B.J. (2011) Interleukin-6 promotes pulmonary emphysema associated with apoptosis in mice. Am. J. Respir. Cell Mol. Biol. 45:720-730.

  • Tye, H., Kennedy, C.L., Najdovska, M., McLeod, L., McCormack, W., Hughes, N., Dev, A., Sievert, W., Ooi, C.H., Ishikawa, T-o., Oshima, H., Bhathal, P.S., Parker, A.E., Oshima, M., Tan, P., JENKINS, B.J.(2012). STAT3-driven Upregulation of TLR2 Promotes Gastric Tumorigenesis Independent of Tumor Inflammation. Cancer Cell. 22:466-478

  • Kennedy, C.L., Najdovska, M., Tye, H., McLeod, L., Yu, L., Jarnicki, A., Bhathal, P.S., Putoczski, T., Ernst, M., JENKINS, B.J. (2014). Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis. Oncogene. 33:2540-2546.

  • Miller, A., McLeod, L., Brooks, G., Ruwanpura, S.M., JENKINS, B.J. (2015) Differential involvement of gp130 signalling pathways in modulating tobacco carcinogen-induced lung tumourigenesis. Oncogene. 34:1510-1519.

  • Jones, G.W., Bombardieri, M., Greenhill, C.J., McLeod, L., Rocher, V., Williams, A.S., Pitzalis, C., JENKINS, B.J.,* Jones, S.A.* (2015) Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. J Exp Med. 212:1793-1802. *Senior co-author.

  • Brooks, G., McLeod, L., Alhayyani, S., Miller, A., Russell, P.A., Ferlin, W., Rose-John, S, Ruwanpura, S.M., JENKINS, B.J. IL-6 trans-signaling promotes KRAS-driven lung carcinogenesis. (2016) Cancer Res. In press.