Molecular Cardiology
Group Head: Associate Professor Christopher Semsarian
Understanding the basic biology of heart muscle function and therefore defining novel ways to treat heart muscle disorders clearly has wider implications for a variety of cardiovascular disorders, including cardiomyopathies, heart rhythm disorders and coronary artery disease. The potential therapeutic boundaries are limitless. Integration of molecular biology, genetic technologies and clinical medicine will ultimately reduce human heart diseases and prolong life. We hope through our research to realise these goals in the coming years.
Research focus
The Agnes Ginges Centre for Molecular Cardiology is focused on the translation of basic laboratory research to improvements in the diagnosis and treatment of patients with heart disease. While there are several lines of integrated research within the program, the unifying focus is the study of cardiovascular disorders which are caused by underlying genetic abnormalities. There are now over 40 cardiovascular diseases which have been identified to be directly caused by primary genetic abnormalities. Despite the escalation in our knowledge of the genetic causes of cardiac disease, little is known about the molecular steps which determine how a defect in the DNA leads to the clinical disease we see in patients. Furthermore, studies have shown marked variability in the degree of clinical expression of the abnormal gene. There are many examples of affected individuals within the one family, who are carrying the same gene (DNA) defect, having vastly different clinical features and outcomes. This suggests modifying factors, both environmental (e.g. exercise, diet) and secondary genetic influences, play an important role in modifying the clinical phenotype in genetic cardiac disorders.
The aims of the research program are to identify new gene abnormalities in patients with heart disease, to understand the molecular basis of how these gene mutations lead to disease and to investigate how these pathogenic mechanisms are influenced by modifying factors. These aims are being addressed in an integrated research program utilising three concurrent sets of studies; in isolated cells, in genetically-modified mice, and in humans with inherited cardiovascular disorders attending the Genetic Heart Disease Clinic at Royal Prince Alfred Hospital. A number of diseases are being studied, ranging from structural heart disorders such as cardiomyopathies to primary arrhythmogenic diseases such as long QT syndrome. A specific area of study is in sudden cardiac death, particularly in the young. These studies include novel gene discovery, genetic diagnosis, understanding disease pathogenesis and initiation of preventative strategies to reduce sudden death in our community.
An example of one of the key diseases which is a focus of the laboratory is hypertrophic cardiomyopathy (HCM) which is the most common structural cause of sudden death in the young, including competitive athletes. HCM is characterised by marked thickening of the heart muscle and occurs in approximately one in 500 people, making it the most common genetic heart disorder known. Our research program has seen and collected clinical information and DNA in over 400 HCM families to enable genetic studies to be performed. To complement the studies in humans, our laboratory has developed two unique transgenic models of HCM, as well as cell culture models to evaluate the cellular effects of specific gene mutations.
