Liver hormone the subject of Premier’s Award for Medical Research

Anaemia and iron-overload disease are completely opposite diseases and the subject of novel research at the Queensland Institute of Medical Research (QIMR), which has been nominated for a prestigious Premier’s Award for Medical Research.

Dr Daniel Wallace is a finalist in the Senior Post-Doctoral Award Category, to be announced on 3 June at the medical research dinner at the Marriott Hotel as part of Annual Medical Research Week.

“Iron is essential for life – however too much or too little can be harmful. According to the World Health Organization up to 80% of the world’s population may have iron deficiency, with 30% having anaemia (low haemoglobin). The virtual opposite to anaemia is a hereditary disorder called haemochromatosis,” said Dr Wallace.

“Haemochromatosis is one of the most common genetic conditions in white people, affecting 1 in 200 Australians. Excess iron in haemochromatosis can lead to liver damage, diabetes and arthritis.”

Most haemochromatosis is caused by mutations in the HFE gene. Other rare forms are caused by mutations in other genes such as transferrin receptor 2 (TfR2). Recent research at QIMR suggests that a hormone produced by the liver – called hepcidin – holds the key to most forms of haemochromatosis and anaemia.

“Hepcidin regulates body iron levels by reducing iron absorption in the intestine. In patients with HFE haemochromatosis, hepcidin levels remain low, making the body think it is iron deficient and hence absorb too much iron. The converse is the case in the anaemia of chronic disease. Inflammation in patients with chronic diseases such as cancer, autoimmune disease and infections can cause hepcidin levels to rise and shut off iron absorption, leading to iron deficiency and eventually anaemia.”

Hepcidin has proved to be a difficult molecule to study and QIMR scientists have produced a specific antibody to help in the research of cell biology and regulation of this important molecule.

“Using this antibody we have shown where hepcidin goes to in liver cells and how it is regulated in mouse models of haemochromatosis and anaemia. In mice with haemochromatosis due to lack of TfR2, hepcidin levels remain low, suggesting that TfR2 as well as HFE are important for the regulation of hepcidin and the maintenance of body iron levels”.

Future research at QIMR will further define the roles of hepcidin and TfR2 with the intention of identifying new therapeutic targets for the diagnosis and treatment of a wide range of iron-associated disorders, both overload and deficiency.

The Queensland Premier’s Awards are part of Annual Medical Research Week organised by the Australian Society for Medical Research.