Cancer and Immune Signalling Research Group
Research Group Head
The 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.
- Role of Toll-like receptors in gastro-intestinal cancers
- Cross-talk between cytokine signalling pathways and inflammasomes in gastro-intestinal cancers
- Regulation of microRNAs by cytokine signalling pathways in gastro-intestinal cancers
- Role of IL-6 signalling pathways in emphysema (COPD) and lung cancer
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.