Project information
Desmin As a Window into Cardiovascular Disease

Desmin is the most abundant intermediate filament in the heart where its role is to interconnect and correctly position multiple organelles such as the mitochondria, contractile apparatus and the nucleus. Furthermore, desmin forms connections at several loci throughout the cell which are necessary for correct cardiomyocyte function, such as the intercalated disc. Mutations in the desmin gene can result in different cardiomyopathies and are often associated with conduction defects, arrhythmia, syncope, sudden cardiac death, and heart failure. Inherited cardiovascular diseases can stem from mutations in proteins that are crucial for proper CM function such as mutations in desmin. More importantly, mutations in the desmin gene can lead to hypertrophic, arrhythmogenic, dilated, or restrictive cardiomyopathy, with variable age of onset (between the first and fourth decade of life) and severity, which may be linked to the position of the mutation. To date, the hallmark and pathophysiological mechanisms underlying the onset and progression of different cardiovascular diseases that terminate in heart failure are poorly understood. This project aims to study the onset and progression of desminopathy as a type of disease “model”, during cardiac differentiation/development which will give us insight into the pathological mechanisms underlying the different cardiovascular diseases and can give us a novel understanding of hear failure. This will be done by using human induced pluripotent stem cells differentiated into derived cardiomyocytes and applying several different techniques to target the problem from different angles. This will help with the new discovery of biomarkers of heart failure, and understanding the onset of disease that can aid in early detection and prevention thus ameliorating patient quality of life and reducing healthcare costs.