THE ROLE OF THE HEPATOCYTE HEDGEHOG PATHWAY IN PROGRESSIVE LIVER INJURY
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
This research plan investigates the role of a pathway, known as the Hedgehog pathway, in the development of liver disease which can result in end-stage scarring known as cirrhosis and even lead to liver cancer (known as Hepatocellular carcinoma). Hepatocellular carcinoma is the globally the third most common cause of cancer death and our research will help to better understand how liver injury develops and how this then leads to liver cancer.
Hookworm Therapy In Coeliac Disease (CeD), Phase 1b
Funder
National Health and Medical Research Council
Funding Amount
$865,002.00
Summary
Parasitic worms have an amazing ability to manipulate the immune system, and our research group recently discovered how they may hold the key for treating inflammatory diseases such as Coeliac Disease. The aim of my research is to further develop this novel therapy in a clinical trial and study the mechanism of how worms control the immune response, including identifying the molecules that the worm produces that could be produced as a pill-based medication for treating coeliac disease.
Pathophysiology Of Functional Dyspepsia: Integration Of Upper Gut Function, Inflammation And A Systems Biology Approach.
Funder
National Health and Medical Research Council
Funding Amount
$748,593.00
Summary
Functional dyspepsia (FD) is an extremely common and costly problem with no cure. We and others have found that inflammation and immune activation play a role in FD but to date no studies have linked these findings with well known diseases markers including disordered sensory and motor function or psychiatric comorbidity. This study will explore the interrelationships between inflammatory and immune mechanisms, disease markers as well as the microbiome. This study could unravel the cause of FD.
Inflammatory Mediators Of Liver Injury In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased ....Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased liver damage in chronic hepatitis C and obesity.Read moreRead less
Muc1 Regulation Of The NLRP3 Inflammasome In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
The mucin Muc1 is an important part of the barrier against infection in the gut, and appears to protect against development of bacterial inflammatory disease. We have identified that Muc1 suppresses activation of the inflammasome (a mechanism by which pathogens cause inflammation). We will now examine how Muc1 does this and explore the importance of this effect on inflammatory disease in the intestine. This may identify novel approaches for protecting against gastric and colorectal cancer.
The Role Of MBOAT7 In Hepatic Inflammation: Implications For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$848,340.00
Summary
When a fatty liver progresses to develop inflammation, patients are at-risk of liver-related morbidity and death. Currently, there are no effective therapies. From human studies, we have discovered that a lipid modifying enzyme (MBOAT7) profoundly regulates liver inflammation. In this proposal, we will obtain a detailed understanding of how the activity of this pathway modulates inflammation. We expect to show that MBOAT7 is a novel ‘druggable’ pathway for the treatment of liver inflammation.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.
Potassium Channel Regulation Of Bacterial-driven Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$576,000.00
Summary
Helicobacter pylori infections cause a chronic inflammation which in some people results in stomach cancer or ulcers. We have used a mouse with natural resistance to H. pylori gastritis to identify a completely novel regulator of the pathology induced by this infection. In this project, we will examine the mechanism by which this regulator protects against disease in mice, and examine its significance in the susceptibility of people to gastric cancer.
Studies Of The Role Of The Hepatocyte In The Response To HCV Infection
Funder
National Health and Medical Research Council
Funding Amount
$513,294.00
Summary
Infection with hepatitis C (HCV) affects 120 million individuals worldwide, and over 200,000 in Australia. HCV-related liver disease is the most common indication for liver transplantation in Australia and rates of HCV-related liver failure and hepatocellular cancer are predicted to increase as the HCV population ages. A new test for the IL28B gene, has shown to be the strongest predictor of cure after treatment. The mechanism of this association is unknown and is the subject of this grant.