Lars Allan Larsen
professor in Molecular Genetics
Brief description of research interests
Congenital heart disease (CHD) represent the most common group of inborn malformations, with an incidence of almost 1% in the population. The aetiology of CHD is complex but with a significant genetic component. Large families with CHD are very rare, thus classical genetic approaches are generally not useful for identification of disease genes and consequently the present number of identified human genes involved in cardiac development and CHD is small. Our research is focused on investigating the genetic aspects of human cardiac development and congenital heart disease.
Heart development is a complex process, which involves establishment of a primitive heart tube, looping of the heart tube, followed by chamber formation, chamber septation and development of the cardiac valves and outflow tract. Development of the heart is coordinated by a significant number of cellular signaling networks like the Hedgehog, WNT, TGF-beta signaling pathways. Furthermore, most of the known human CHD disease genes are involved in different aspects of cellular signaling. Thus, we are also interested in exploring the mechanisms and organelles which regulate signaling transduction during heart development and cardiomyogenesis, for example the primary cilium.
We explore different genomic strategies for identification of genes, genomic regulatory regions and molecular networks involved in cardiac development and disease. We investigate the function of the candidate genes or signaling pathways by expression analysis in embryonic tissues and functional assays in cell models and zebrafish. Identification of genes associated with cardiac development and CHD is likely to have an impact on early diagnosis and prevention of CHD and may also provide a basis for development of new drug therapies e.g. for minor cardiac defects like small atrial- and ventricular defects.
Furthermore, identifying and understanding molecular mechanisms in human cardiac development, especially the subset of genes and molecular networks which regulate cardiomyogenesis is likely to have an impact on the development of therapeutic means for regeneration of cardiomyocytes in myocardial infarction and congestive heart failure.