Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Characterization Of Novel, Colitis Associated Pathobionts To Identify Therapeutic Targets In The Host Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$684,609.00
Summary
Applying cutting edge methods to grow bacteria from the human gut, we have identified three species, two previously unknown, that are found in many inflammatory diseases including Inflammatory bowel disease, colorectal cancer and in cancer immunotherapy patients who experience colitis. By characterizing these bacteria and the immune response in human cells we are seeking to discover novel targetted methods to prevent colitis and gastrointestinal inflammation.
E. coli is a normal inhabitant of the human intestine, but some varieties can cause serious infections that may lead to the premature death of children, especially in less developed countries. The aims of this study are to learn more about these harmful varieties of E. coli and to enhance our ability to detect them in samples from patients and the environment.
Blood Serum MicroRNA Biomarkers For Oesophageal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$495,433.00
Summary
Oesophageal adenocarcinoma (OAC) is the 6th commonest cause of cancer deaths in the Western World, and is increasing in incidence. In Australia most patients present late and require risky treatments with a low cure rate. There is a big difference in survival between individuals presenting early vs. late. Better methods to detect cancer early or detect pre-cancer will improve outcomes. Our research will develop a blood test for identifying individuals with early OAC to allow earlier treatment.
Hypoxic Regulation Of Integrin Beta1 During Mucosal Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$318,104.00
Summary
Very little is currently known about how healing is initiated in the gut. Further understanding may allow us to improve the treatment of IBD wounding and allow new therapies to control the disease. Our work examines the role of an adhesion protein, ?1 integrin, important in the repair of intestinal wounds. Understanding the mechanisms of how ?1 integrin is involved in wound healing may allow the rational design of therapies to aid or accelerate wound healing in inflammatory disease.
Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Modulating Gastrointestinal Function For Control Of Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$883,469.00
Summary
It is now recognized that gastrointestinal function, particularly the rate that meals empty from the stomach, and the secretion of hormones from the small intestine in response to nutrients, is fundamental to blood glucose control in people with diabetes. This project seeks to understand how these processes can best be modified by dietary or pharmaceutical means to improve blood glucose control and thereby prevent complications in type 2 diabetes
Irritable Bowel Syndrome (IBS) is one of the leading causes of chronic pain both world-wide and in Australia for which there is a lack of treatments. Chronic pain arises from nerve fibres in the colon wall, which fail to 'reset' back to normal following inflammation. Targeting these nerve endings with drugs is a key advance in IBS treatment. This project will identify selective oxytocin analogues that act in the colon to lower pain in sensory nerves thus providing efficacious pain relief in IBS.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
CCR9 Expressing T Helper Cells In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We have identified a unique subset of immune cells in autoimmune lesions named Tccr9 cells. You find these cells in the gut, but when the body shifts into disease mode, Tccr9 cells disseminate to the accessory organs of the digestive system. Understanding the relationship between gut Tccr9 cells and the Tccr9 cells that contribute to chronic inflammation and autoimmunity is the focus of this research proposal.