Liver disease remains a major global health burden, yet progress in understanding human-specific liver development and pathology is limited by the lack of physiologically relevant in vitro models. This project aims to generate functional liver organoids from human pluripotent stem cells and apply integrated multiomics analyses to dissect the molecular mechanisms governing liver maturation, homeostasis, and disease. We will establish robust differentiation protocols to produce three-dimensional liver organoids containing hepatocyte-like cells and supporting non-parenchymal populations. These organoids will be characterized for structural organization, metabolic activity, and liver-specific functions. To comprehensively map cellular identity and developmental trajectories, we will perform multiomics profiling, including single-cell transcriptomics, epigenomics, and proteomics. Integration of these datasets will enable high-resolution reconstruction of regulatory networks that drive hepatic lineage specification and functional maturation. In parallel, we will apply perturbation strategies—such as pathway modulation and disease-relevant stressors—to model key aspects of liver injury and metabolic dysfunction. Comparative multiomics analysis between healthy and perturbed organoids will identify critical signaling pathways, transcriptional regulators, and metabolic programs associated with disease initiation and progression. The outcomes of this project will provide a scalable human liver organoid platform and a rich multi-layered molecular atlas of liver development and pathology. This work is expected to advance our understanding of human liver biology, facilitate discovery of novel therapeutic targets, and establish a foundation for personalized disease modeling and drug screening. Ultimately, the integration of stem cell–derived organoids with multiomics technologies offers a powerful approach to bridge the gap between basic liver research and translational applications.