Human Pluripotent Stem Cell-derived 3D organoids provide an unprecedented avenue for disease modelling, drug discovery and potential cell replacement therapies for unmet clinical needs in human diseases. However, organ development is a complex morphogenetic process guided by core transcriptional machinery and microenvironment niche that play critical roles in progenitor specification, differentiation and maturation. The major limitations are recapitulating those endogenous developmental pathways and cellular interactions in the dish to develop physiologically relevant hPSC-derived 3-D organoids for studies and therapies. We are utilizing expertise in Developmental and Stem Cell Biology, advanced Molecular Biology, Biochemistry, Cellular and Systems Physiology, CRISP-Cas9 gene editing and cutting-edge genomic technology (omics profiling- single cell biology, metabolomics) to get mechanistic insight of organ development, factors leading to pathophysiology, tissue engineering and to develop novel therapeutic approaches for the management and cure of cardiovascular diseases and diabetes.