Research Projects

Conotruncal heart defects (CTDs) are cardiac structural malformations affecting approximately 25% of congenital heart defects (CHDs). Despite their multifactorial nature, genetic factors have been found to contribute significantly to the pathogenesis of CTDs. Despite extensive research, most studies focus on epidemiology, clinical aspects, and surgical interventions. The molecular mechanisms of CHDs are largely based on animal models, which do not accurately reflect the cardiac phenotype present in the patient. Additionally, there are significant differences in genetic factors, genomic complexities, and electrophysiological properties between mouse and human hearts. To study the disease pathogenesis, there is a pressing need to generate patient-derived in-vitro disease models with the same genetic background and exact genetic variant representing the human cardiac phenotype. This study aims to generate CTD patient-specific human induced pluripotent stem cell (ps-hiPSC) models to investigate the cellular and molecular genetic mechanisms of cardiogenesis. Skin fibroblasts or PBMCs from CTD patients will be isolated, reprogramed into iPSCs, and differentiated into cardiomyocytes (CMs) using standard protocols. Isogenic cell lines will be generated using CRISPR-Cas9 gene-editing technology. These patient-specific cellular models will enable the study of disease pathophysiology, investigate the role of novel genetic variants or candidate CTD genes, and study differential signaling pathways and metabolite status using comparative proteomics, phosphoproteomics, and metabolomics analysis. This multi-omics approach will be crucial in identifying potential disease biomarkers for early diagnosis and developing novel therapeutic strategies for effective management of CTD patients.