Role of the ADAM17 protease in lung disease (emphysema, cancer) and pancreatitis

Role of the ADAM17 protease in lung disease (emphysema, cancer) and pancreatitis is a Research Project for the Cancer and Immune Signalling Research Group, under the Centre for Innate Immunity and Infectious Diseases.

Project Leaders

ciiid-image2The A disintegrin and metalloproteinase 17 (ADAM17) protease, also known as tumour necrosis factor-α (TNFα)-converting enzyme (TACE), is responsible for the protease-driven shedding of more than 70 membrane-tethered cytokines, growth factors and cell surface receptors. Among these, the soluble interleukin-6 receptor (sIL-6R), which drives pro-inflammatory and pro-tumourigenic IL-6 trans-signaling, along with several EGFR family ligands, are the best characterised. This large repertoire of substrates processed by ADAM17 places it as a pivotal orchestrator of a myriad of physiological and pathological processes associated with the initiation and/or progression of cancer, such as cell proliferation, survival, regeneration, differentiation and inflammation. This project aims to define the molecular basis by which ADAM17 drives the pathogenesis of these disease states by employing a combination of in vivo mouse disease models, together with validation studies using clinical biopsies.

Ross Vlahos/Steven Bozinovski (RMIT University)
Stefan Rose-John (University of Kiel, Germany)
Irit Sagi (Weizmann Institute, Israel)
Matthew Freeman (Oxford University, UK)