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Too little or too much of the essential element iron is the cause of some of the most common disorders affecting humans. These include iron overload, anaemia, and anaemia of chronic disease. This project examines the genes and the roles they play in regulating iron levels in the body, and the consequences to the individuals when they are mutated. Ultimately I intend to develop therapeutics and diagnostics which will help early diagnosis and effective treatment of these disorders.
This proposal is aimed at improving the health of people with “Disorders of Iron Metabolism”. It focuses on the iron-related diseases hereditary haemochromatosis and colorectal cancer, as well as liver disease, chronic kidney disease and malnutrition. Outcomes from these studies are expected to identify how iron metabolism is impaired, the clinical consequences and new strategies for the prevention and treatment of iron-related diseases.
Iron is essential in the diet but it is also toxic when present in excess, so both iron deficiency and iron overload can have significant clinical consequences. I will investigate the basic mechanisms by which the body acquires iron and how iron can lead to toxicity. The goal of these studies is to provide more effective iron supplements and to improve diagnosis and treatment of iron-related diseases. Iron metabolism in pregnancy, infants and respiratory diseases will be a particular focus.
My major goal for the past 20 years has been to understand how hormones such as gastrin stimulate the development of gastrointestinal cancer. One approach has been to define the intracellular signalling pathways by which gastrins enhance cell growth. Our discovery that iron is essential for the biological activity of gastrins may allow the development of novel therapies for colon cancer and iron overload.
Brain Metal Neurochemistry: Mechanism-driven Drug Discovery For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Alzheimer’s disease (AD) is a complex disease where certain proteins congeal in the brain and metals accumulate. This project investigates the function of the proteins in microscopically transporting the metals. It will also look for tests that predict the onset of AD by measuring iron and iron related proteins by using special brain imaging (MRI), and measurements in spinal fluid. Finally, it will test drug candidates that target the metals, in animal models of AD, and in early clinical trials.
Liver Injury And Iron Homeostasis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Iron disorders and liver disease are a significant burden on society, affecting many in the prime of their life. Disordered iron metabolism also plays a significant role in many disorders and diseases including cancers, neurodegenerative and iron overload disorders, and anaemia associated with chronic disease. My objective is to understand the molecules and mechanisms involved, and to develop strategies and reagents to diagnose, prevent and treat liver and iron-related disease.