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Inflammatory Bowel Diseases Team

Team leader Prof Timothy Florin Team members Rachel Adams, Research Assistant Dr Rai Eri, Research Fellow Iulia Oancea, Masters Student Chin Wen Png, PhD Student Inflammatory bowel diseases (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD) affect 50,000 Australians. They are a major cause of chronic disease in the gut causing considerable personal distress.  Persons with IBD have an increased risk of bowel and bile duct cancers and some types of arthritis. IBD can affect children and adults first manifesting most frequently in the second and third decades of life. The diseases entail inflammation in the intestine that is amplified by recruitment of the immune system. The initiating factors that cause the inflammation are not known and cures remain to be discovered. Aims: Our work is focused on: •    Understanding why IBD occur •    Developing better ways to treat them •    Helping to make the lives of IBD patients better Projects Mucolytic bacteria and IBD The mucus barrier is the primary defence of the intestine against infection from bacteria and viruses. We have novel data that indicate that mucolytic bacteria are increased in IBD. We are studying the relevance of their mucolytic activity in IBD. Endoplasmic reticulum (ER) stress and inflammation We have novel evidence that UC is caused by a defect in quality control of the manufacture of mucin, the dominant protein forming the intestinal mucus barrier. The mucin protein is manufactured by the endoplasmic reticulum - organelles in the cells that line the intestine. The project is divided into researching – •    the relationship between ER stress and chronic inflammation •    the relationship between intestinal bacteria, ER stress and mucus •    defining the spectrum of ER stress in UC and CD •    genetic predispositions to ER stress in the intestine •    exploring the connexion between ER stress and intestinal cancers •    ways to reduce ER stress in the intestine Better use of thiopurine therapies to prevent amplification of inflammation by the immune system Thiopurines discovered by 1989 Nobel Prize winning chemists, Elion and Hitchings, are excellent therapies despite known side-effects (that can be avoided with proper use).  They are not only useful for IBD, but also autoimmune diseases, rheumatoid arthritis, to aid organ transplantation and to treat leukemias. They are vastly cheaper than alternative therapies. Unfortunately, approximately 30% of patients cannot use them because of side-effects or insufficient response. We are: •    Discovering ways to prevent the accumulation of toxic metabolites of thiopurines •    Discovering why there is a much higher risk of life-threatening liver disease with one of the thiopurines, 6-thioguanine, which is otherwise superior to the more commonly used azathioprine or 6-mercaptopurine