Using Nanotechnology To Improve The Therapeutic Efficacy Of Iron Chelators
Funder
National Health and Medical Research Council
Funding Amount
$692,769.00
Summary
Iron loading disorders (such as thalassaemia) represent an important class of human disease. As part of the treatment for these diseases, the iron needs to be removed and this is often done using iron-binding drugs known as iron chelators. Current chelators are not ideal due to side effects or onerous delivery methods. The goal of this project is to use nanotechnology to develop more effective ways of delivering chelators to improve their effectiveness and reduce toxicity.
Understanding The Structure/function Relationships Of The Iron Regulatory Peptide Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
This project seeks to understand the interactions between the peptide hormone hepcidin and its receptor and use this information to develop new drugs. Hepcidin is the major iron-regulatory hormone in humans and a range of iron-related diseases are caused by incorrect levels of this hormone. Many Australians are affected by these diseases so the development of hepcidin-based treatments has the potential to have significant impact on the overall health of the community.
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.
Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.
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
Venesection Or Expectant Management For Moderate Iron Overload In HFE Related Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$853,109.00
Summary
Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.
Tissue Ferritin Acts As A Proinflammatory Mediator Of Hepatic Fibrosis In Chronic Liver Disease Via Multiple Receptors In Hepatic Stellate Cells Responsible For Both Binding And Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$777,887.00
Summary
Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology, the cells responsible for liver scarring (fibrosis) in Haemochromatosis. This proposal will identify the receptor responsible for eliciting ferritin's proinflammatory action and assess its role in fibrosis. This study will have implications in chronic liver diseases of varying aetiologies where elevated serum ferrritin is associated with inflammation.
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.