C01-Modelling of a cardiac valve and aortic aneurysm disease using human induced pluripotent stem cells (hiPSCs)

Cardiac valve diseases and aortic aneurysms (AA) can be caused by genetic mutations. For example, recent findings from our consortium reveal that a single nucleotide polymorphism in the MUC4 gene is associated with an increased risk for bicuspid aortic valve (BAV) formation. Similarly, somatic mutations in hematopoietic stem cells leading to clonal haematopoiesis of indeterminate potential (CHIP) correlate with an increased risk of cardiovascular disease, and mutations in the elastin microfibril interfacer 1 (EMILIN1) gene result in early postnatal vascular malformations and AA. Since the pathogenic mechanisms of these mutations are challenging to study in animal models, we will take advantage of gene-edited hiPSCs and 2D and 3D differentiation approaches to investigate those disease mechanisms, identify novel targets, and probe experimental therapies.