Department: Paediatrics, University of Toronto
Our lab is interested in developing stem cell models for childhood onset heart disease. The process of cardiac differentiation of ES and iPS cells recapitulates fetal cardiac embryogenesis. We recently demonstrated that alterations in cellular microenvironment during cardiac differentiation of hES cells recapitulates the pathology seen in fetal cardiac malformations. We are using this platform to explore the mechanisms by which chemical and environmental exposures adversely impact cardiac development and differentiation. Our lab is also developing cellular models of disease using patient-derived iPS cells. We recently generated vascular smooth muscle cells from a patient with Williams-Beuren syndrome that recapitulates the abnormal proliferative vascular smooth muscle phenotype in this disease. This phenotype was successfully rescued using candidate drugs. Our lab is now developing a cellomics and live cell imaging based platform for high-throughput screening of drug and chemical compound libraries for drug discovery for vascular disorders. Through patients enrolled in the SickKids Heart Centre Biobank, additional patient-derived skin fibroblasts are being reprogrammed for generating cardiac disease models, particularly cardiac genetic disorders, through local and international collaborations with the eventual goal of personalized therapeutics for childhood onset heart disease.