The major research interest in the Chen Laboratory is to apply human pluripotent stem cell (hPSC)-derived cells/organoids to model human diseases and perform drug screens toward development of novel therapeutics. We have identified many small molecules controlling stem cell fate decision using high throughput/content chemical screens. By combining gene targeting, directed differentiation, human organoids, and humanized mouse models, we have established several unique models to systematically explore the role of genetic and/or environmental factors in disease progression. We establish proof-of-principle that “disease in a dish” models that can be adapted to high throughput/content screening platforms and to discover drug candidates for precision therapy.