Current knowledge clearly reveals a more complex pathophysiologic basis for disease development, including a role for secondary disease-modifiers that, once identified, can serve as therapeutic targets. As the toxicity of the mutations and the secondary disease-modifiers are largely unknown, clinicians are unable to perform proper risk stratification or to initiate rational preventive therapy. As a result, mutation-carriers at risk may be undertreated, while carriers at low risk may receive drugs that cause negative side-effects or expensive defibrillators that will never fire. As the number of newly identified mutations in genes encoding the sarcomere and its stabilizing proteins in cardiomyopathy patients and their family members is still rising, there is an urgent need to improve risk stratification in healthy individuals carrying a sarcomere mutation and to design therapies to prevent and/or delay onset of cardiomyopathy.

To unravel the complex cardiomyopathy pathophysiology, we believe in a tight collaboration between the different actors involved in this field, including (clinical) geneticists, cardiologists, cell biologists and physiologists. Dosis bundles expertise within the different research fields and links clinical studies with mechanistic insights obtained from molecular and functional studies in human cardiac muscle samples, cell systems and animal models, which cover the initial but also the advanced stages of inherited cardiomyopathies. Furthermore, established cardiomyocyte and Drosophila models are utilized to conduct mechanistic studies and drug screening.

Lead investigators