Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence ind ....Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence indicate that BAFF may be important in T cell biology. Current studies suggest that BAFF exerts a pro-inflammatory effect upon T cell responses. Surprisingly then, when we examined the role of BAFF upon T cell function in vivo in the context of the allo-immune response, we found that ~60% of BAFF transgenic mice failed to reject a fully-mismatched allograft. Intriguingly, BAFF transgenic mice exhibited an increased number of CD4+ CD25+ Foxp3+ cells in the periphery and in vivo depletion of these CD25+ cells restored the ability of BAFF transgenic mice to reject an allograft. We hypothesize that BAFF plays a potentially powerful anti-inflammatory role in regulating certain T cell dependent immune responses. Our data suggests that BAFF can modulate T cell function by effecting T cell regulation.Read moreRead less
Cholestasis And Hepatocyte Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,967.00
Summary
The aim of this project is to understand the consequences of long-term cholestasis or impaired bile excretion/flow on normal liver cells (hepatocytes) and to test whether specific bile acids can cause irreversible damage to hepatocytes leading to their transformation into pre-malignant cells and hepatocellular carcinoma (primary liver cancer). The results from this project will inform new strategies in screening, prevention and treatment of liver cancer in children and adults with cholestasis.
Significance Of Microparticles In The Pathogenesis Of Liver Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
The overall aim of the project is to investigate the significance of microparticles in liver ischemia reperfusion injury (IRI). IRI causes damage to donor livers stored in preparation for liver transplantation. We postulate that microparticles released from the liver are critical in this form of injury. The expected outcomes are novel insights into liver IRI with the aim of developing new approaches to prevent liver damage during liver surgery, transplantation and shock.
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.
P53 And Hepatocyte Proliferation In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$331,360.00
Summary
The aim of this project is understand how loss of control of p53, a tumour suppressor gene, in liver cells causes the transformation of normal liver cell (hepatocyte) to ‘rouge’ pre-cancerous cells in hepatocellular carcinoma (HCC) or primary liver cancer. We will test novel therapies to restore p53 function in liver cells in order to prevent or retard the development of HCC in patients with cirrhosis and those ‘at risk’ of this rapidly increasing fatal cancer in Australia.
MERTK Receptor Tyrosine Kinase: A Novel Therapeutic Target For Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$870,972.00
Summary
Hepatic fibrosis is the principal cause of liver-related morbidity and mortality, for which there are no effective therapies. Thus, there is an urgent and unmet need to identify new targets to treat liver fibrosis. We have demonstrated for the first time, that liver fibrosis correlates with elevated hepatic expression of MERTK, a receptor tyrosine kinase. This project will explore whether MERTK function can be exploited to target and reverse liver fibrosis