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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.
Assessment Of Oxidant Stress And Mitochondrial Dysfunction In Young Adults With Iron Loading Diseases
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Disorders of iron metabolism are particularly prevalent in Australia and the consequences of excess iron can be severe. Liver disease is frequently associated with iron loading. The commonest form of iron loading can be treated readily, but it is unclear when the first signs of tissue damage occur and thus at what stage treatment should commence. This project will examine in detail the relationship between body iron levels and signs of tissue damage in young subjects with iron loading disease.
Defining Iron And Haem-induced Pro-carcinogenic Pathways Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
Colorectal cancer is very common in Western society. Population studies have reported that high consumption iron-containing foods and red meat, the latter being a source of both haem and iron, are risk factors for colorectal cancer. This study will identify the levels of dietary haem and iron that promote colorectal cancer development. Also, it will determine the mechanisms and relative contribution of iron and haem to pro-carcinogenic pathways that result in colorectal cancer.
The Role Of Cyp2e1, Alcohol And HCV In Modulation Of Hepatocyte Homeostasis HCV Replication And Resistance To Interferon
Funder
National Health and Medical Research Council
Funding Amount
$455,520.00
Summary
Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerfu ....Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerful mediator of liver injury called tumour necrosis factor alpha. Furthermore we have shown that alcohol metabolism by Cyp2e1 results in an increase in HCV replication and negatively impacts on the anti-viral action of interferon. The studies contained within this proposal aim to build on these exciting new insights by attempting to identify new mediators and mechanisms of liver disease as a consequence of Cyp2e1 expression, alcohol and HCV replication. We will also examine the molecular mechanisms by which alcohol potentiates HCV replication. These studies will assist in developing therapeutic strategies that will benefit alcohol- and HCV-related liver disease.Read moreRead less