Division Head: Professor Robert Graham
The Molecular Cardiology Program aims to understand both the molecular signaling pathways that operate within the heart and the molecular basis of inherited genetic heart diseases. The Program consists of two laboratories, the first established at the inception of the Institute is headed by Professor Robert Graham, and the second, established in 2000, is headed by A/Professor Diane Fatkin.
Professor Robert Graham's Laboratory
Professor Graham's Laboratory is focused on understanding the structure and function of G-protein-coupled receptors. These receptors, already the targets of over 50% of all known drugs, are present on the surface of every major tissue and organ of the body, where they play an important role in regulating their functions in response to a variety of different stresses.
In particular, the laboratory is interested in a1-adrenergic receptors and a related novel G-protein discovered by this laboratory, termed Gh (or tissue transglutaminase). Both may play an important role in the development of abnormal thickening of heart muscle - a condition known as cardiac hypertrophy - and in the development of heart-rhythm disturbances (cardiac arrhythmias). To elucidate the functions of these proteins, the laboratory utilises a variety of techniques, including molecular modeling, site-directed mutagenesis, and biophysical studies. Another focus of the laboratory is to understand the causes of cardiac hypertrophy - a major risk factor for stroke and death in our community.
Professor Graham's Laboratory is interested in the signaling pathways, which operate under conditions of hypertrophy, and the role that growth factors may play in this disease. Studies of the molecular and cellular events underlying an inherited form of cardiac hypertrophy are also being performed in collaboration with Dr Fatkin's laboratory. Finally, Professor Graham is spearheading a major clinical trial of adult stem cells for the treatment of patients with severe coronary artery disease.
Stem Cell Clinical Trials
Headed by Professor Robert Graham and in collaboration with St. Vincent's Hospital, the Institute is running a controlled clinical trial to determine if adult stem cells from bone marrow can improve heart function in patients with severe angina.
Severe angina is an often debilitating disease caused by insufficient blood supply to the heart that results from severe blockages or total obstruction of the coronary arteries. As a result the sufferers have decreased heart function, which means that the heart cannot pump enough blood around the body. At its worst, there is no treatment and the patient's life is significantly reduced, both in length and quality.
The trial involves recruitment of adult stem cells (immature muscle cells which have not yet fully differentiated) from the bone marrow to the heart, where it is hoped they will start the process of repair by leafing to the growth of new blood vessels to improve both blood supply to the heart and its functioning.
A/Professor Diane Fatkin's Laboratory
The major focus of A/Prof Diane Fatkin's group is the identification of genes that cause disturbances of heart contraction and rhythm, and the elucidation of the functions of the genes, that when abnormal, causes these disorders.
In particular, the laboratory is interested in a heart muscle disease called dilated cardiomyopathy (DCM). This disease is characterised by dilation of the heart and abnormal contraction of heart muscle, and in 20-35% of cases is due to a defective (or mutated) gene that can potentially be passed on from an affected person to their children. Studies of such families with DCM, as are being performed by A/Prof Fatkin's group, should allow the identification of new disease-causing genes, and hopefully, will eventually lead to new treatments for these disorder. Currently, when severe, such disorders can only be treated by heart transplantation. In large families, genetic linkage studies are performed, while candicate genes are evaluated for mutations in small families.
Atrial Fibrillation (AF) is a heart rhythm disorder, which involves rapid atrial activation, and has been a major cause of morbidity and mortality in society. The molecular basis of DCM and AF remain largely unknown. A/Professor Fatkin's group investigates the molecular basis of these diseases through a number of cutting-edge techniques in the fields of human genetics and cell culture, and also using exciting new zebrafish animal models.
Professor Terry Campbell & A/Professor Jamie Vandenberg's Laboratory
The coordinated spread of electrical impulses down the heart is required for it to pump blood efficiently. If this process becomes disordered the heart pumps inefficiently or may even stop, resulting in sudden death. The aim of the work in the Mark Cowley Lidwill Research Program in Cardiac Electrophysiology is to investigate situations where these electrical impulses become disordered and to understand the causes of such conditions.
Electrical impulses in the heart are controlled by ion-channels, molecular structures that facilitate the passage of ions into and out of cells. We have five major projects looking at different aspects of how ion channels work and how disturbances in ion channel function affects the heart: 1. Genotype-phenotype relationships in the congenital Long QT syndrome. 2. Structure-function studies of HERG K+ channels. 3. Molecular basis of drug binding to hERG K+ channels. 4. Genotype-phenotype relationships in Familial Atrial Fibrillation. 5. Structure-function studies of Two pore K+ channels
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