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Developing intestinal buds, colours highlight the proteins involved in growth

Dr Tracy Putoczki presents her research findings into targeting cytokines in inflammatory diseases with a focus on Interkeukin-11.

Defining the mechanism of signalling by interleukin-11

Interleukin (IL)-11 is a member of the IL-6 family of pleiotropic cytokines. IL-11 signalling is initiated following binding to its membrane bound, cell-type specific receptor, IL-11R. This binary complex engages a transmembrane receptor called GP130, inducing dimerisation and activation of the transcription factor STAT3. STAT3 has been implicated in the maintenance of a tumour-promoting microenvironment, and persistent STAT3 activation is a feature of many human cancers of both haematopoietic and epithelial origin. We were the first to solve the structure of the human IL-11 ligand. We are now using molecular and structural biology techniques to define the function of the authentic signalling complex.

Examining how cytokines promote tumour growth, invasion and metastasis

A common feature of all tumours is the bi-directional interactions between tumour cells and the stroma, whereby tumour cells can stimulate the inflamed stroma, which in turn can enhance the malignant traits of tumour cells. This self-amplifying feedback loop is fuelled by cytokines. For this reason, the concept of combating tumour progression, through inhibition of growth promoting cytokines present in the tumour microenvironment is becoming of great therapeutic interest. We are combining laboratory models and patient clinical data to understand the role of cytokines in stomach, colon and pancreatic cancer and how they promote resistance to current standard-of-care therapies.

Understanding the link between inflammatory bowel disease and colorectal cancer

Colorectal cancer (CRC) is the forth most common cause of malignancy worldwide. Alarmingly, the highest incidence rates occur in Australia, where CRC is the second most common cause of cancer-related deaths. Despite significant progress in our understanding of the familial basis of this disease, genetic predisposition only contributes to ~20% of CRC cases. The remainder are attributed to numerous environmental factors, including chronic colonic inflammation. We are establishing new imaging technologies, and laboratory models to characterise novel proteins that are associated with human inflammatory bowel disease and CRC.