Dissecting The TMPRSS6 Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia
How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.
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.
Role Of A Nuclear Receptor Coregulator In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$623,152.00
Summary
Colorectal cancer is a major burden to society. We have identified a protein called SLIRP that is altered in colorectal cancer, and this project will investigate how SLIRP regulates growth of these cancer cells. We envisage that the results of this project will lead to new ways to reduce colorectal cancer cell growth, and potentially a new marker to help in diagnostic and treatment decisions.
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.
Role Of Non-transferrin Bound Iron In Iron Overload Disease
Funder
National Health and Medical Research Council
Funding Amount
$669,504.00
Summary
Plasma non-transferrin bound iron (NTBI) levels are elevated in iron overload disorders. Excess NTBI has serious health consequences as it is toxic and may induce cellular dysfunction and injury. We will investigate the molecular mechanisms by which NTBI transport is regulated, the contribution of NTBI to the development of iron overload and its impact on oxidative-mediated liver and heart injury in iron overload conditions associated with Hereditary Haemochromatosis and thalassaemia.
Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.
Cellular Cross-talk Between Liver Progenitor Cells And Hepatic Stellate Cells Is Required For Hepatic Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$618,517.00
Summary
Deloitte Access Economics data proposes the total economic burden of liver disease in Australia in 2012 was >$50 billion. This study will identify how the liver heals itself by inducing liver cell populations which interact to regenerate damaged liver tissue in chronic liver disease. This knowledge may lead to the development of novel therapeutic interventions for the treatment of liver scarring and liver cancer, and to assist in normal liver regeneration following chronic liver disease.
Tissue Ferritin Is A Damage-associated Molecular Pattern (DAMP) In Inflammasome-induced Inflammation Associated With Hepatic Stellate Cell Activation And Fibrogenesis In Chronic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$783,612.00
Summary
We have generated considerable evidence for a role for tissue ferritin as a mediator of inflammation associated with liver fibrosis (scarring) These highly novel and innovative studies will assist in identifying pathways involved in the proinflammatory phenotype of hepatic stellate cells (scar-forming cells in the liver) in chronic liver disease and thus will greatly aid in understanding how liver scarring occurs in chronic liver disease.
HFE-associated Steatohepatitis: Mechanisms And Therapies
Funder
National Health and Medical Research Council
Funding Amount
$650,813.00
Summary
Iron and fat alter normal iron metabolism and cause more severe disease in combination. In this study we will study the relationship between liver disease caused by increased body iron and the consumption of excess fat and the causal mechanisms. We will then examine new therapies for the treatment of iron-associated fatty liver disease.