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 CJ, Rose-John S, Lissilaa R, Ferlin W, Ernst M, Hertzog PJ, Mansell A, Jenkins BJ (2011) IL-6 Trans-Signaling Modulates TLR4-Dependent Inflammatory Responses via STAT3. J. Immunol 186:1199-1208.

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

  • Tye H, Kennedy CL, Najdovska M, McLeod L, McCormack W, Hughes N, Dev A, Sievert W, Ooi CH, Ishikawa T-o, Oshima H, Bhathal PS, Parker AE, Oshima M, Tan P, Jenkins BJ (2012) STAT3-driven Upregulation of TLR2 Promotes Gastric Tumorigenesis Independent of Tumor Inflammation. Cancer Cell 22:466-478.

  • Kennedy CL, Najdovska M, Tye H, McLeod L, Yu L, Jarnicki A, Bhathal PS, Putoczski T, Ernst M, Jenkins BJ (2014) Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis. Oncogene 33:2540-2546.

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

  • Jones GW, Bombardieri M, Greenhill CJ, McLeod L, Rocher V, Williams AS, Pitzalis C, Jenkins BJ,* Jones SA* (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 PA, Ferlin W, Rose-John S, Ruwanpura SM, Jenkins BJ. IL-6 trans-signaling promotes KRAS-driven lung carcinogenesis (2016) Cancer Res In press.