Elastic fibers provide resilience and elasticity to the soft tissues of the body Age-related disease, including arterial aneurysm formation, pulmonary emphysema, and several eye diseases, often associates with progressive disintegration of the elastic fibers

To understand normal elastic fiber biology, we study cutis laxa (CL) syndromes These rare monogenic connective tissue disorders are paradigms to study elastic fiber assembly Patients show a loose, redundant, wrinkled skin that may associate with aneurysm formation, emphysema, skeletal, ophthalmological and/or neurological defects Highly diverse underlying defects cause severe fragmentation of the elastic fibers resulting from aberrant extracellular matrix assembly, impaired intracellular transport and mitochondrial deficiency However, the pathophysiology remains largely unexplored

Firstly, we will reclassify the different CL entities based on clinical presentation and electron microscopy findings of skin biopsies and formulate management guidelines This should be a great asset for clinicians Secondly, we will identify novel genetic causes in molecularly unsolved CL patients Thirdly, we will investigate the common and divergent disease mechanisms on patient fibroblasts and in zebrafish models for molecularly diverse CL subtypes As a whole, the data will provide novel insights on elastic fiber assembly and homeostasis