Head – Xiao-Jun Du
Du’s current research group was established in 1995, when, in a first for Australia, he shifted his research focus from classical models to genetically modified mouse models: animals which have been genetically altered, allowing the close examination of the effects of specific genes in heart disease. Du’s research is pivotal to the work at Baker IDI: application and discovery in vivo is critical to understanding genetic and molecular mechanisms.
The contribution of these new classes of genetically modified mice to cardiovascular disease research cannot be overstated. Eliminating or over expressing a gene in a mouse and then inducing a range of conditions from diabetes to heart attack in the animal allows detailed study of the behaviours of that gene and the mechanisms affected by it. Crossing these animals would also allow for research on gene interactions.
Du’s stamp on this field has been the development of intricate research techniques on these animals. The heart of a mouse is roughly the size of a soybean and weighs about 0.1 gram. Microsurgery, open chest surgery and other sophisticated procedures such as heart catheterisation and echocardiography, the estimation of the size and shape of the heart, are infinitely complicated by the very tininess of the organ. Performing these procedures is an exacting technical process and one that Du has pioneered. His is the only group in Australia capable of performing this surgery and one of only a few in the world with such expertise. Du is regularly called upon to train other scientists and internationally his skills are in high demand.
The importance of mice to cardiovascular disease research was also highlighted with the discovery in 1997 by Du’s team that the mouse was the only animal model to develop one of the most serious complications known in heart attack: rupture of the ventricular wall. This event almost always leads to sudden death and accounts for 5 - 25 per cent of total deaths during the acute phase. While many other areas of heart disease have seen great improvements, this, one of the most malignant complications, has been out of reach of researchers because none of the other species used in heart research develop ruptures after heart attack is induced.
This significant discovery has led to ongoing research by Du and his lab into ways of eliminating the risk of this complication - understanding why ruptures occur in the first place and which drug treatments might stop them occurring.
Another key research area for Du is on the peptide hormone relaxin, a study that is continuing and expanding in its collaboration with the Howard Florey Institute in Melbourne. While it has long been associated with reproduction, its increase in the female body in pregnancy allowing the enlargement of the uterus and the safe delivery of a baby, it appears that relaxin, which breaks down collagen in the reproductive system, may also help prevent heart disease.
Until now however, the function of this hormone had only been investigated in relation to the reproductive system. Developing a model of mouse without the relaxin gene, Du discovered its absence causes a build up of scar tissue in the heart, a condition known as fibrosis and the hallmark of heart disease in humans. Fibrosis is one of the body’s most basic responses to heart disease and greatly contributes to the decline of heart function. The importance of reducing fibrosis is well documented but as yet there is no effective drug treatment. Most recent research has found that treating animals with relaxin for a period as short as two weeks significantly reduced their fibrosis. Plans are now underway for a clinical trial.