Our ability to reprogram somatic cells to a pluripotent state (from which differentiation into various cell lineages can be induced), as well as the capability to isolate and propagate adult stem cells from human tissues, are revolutionizing both our understanding of basic stem cell biology as well as approaches to disease modeling. While the technology is still at its infancy, we have begun to witness the potential of stem cells in multiple applications ranging from regenerative therapy to disease modeling in a dish. To harness the full capacity of these stem cells, we aim to address two fundamental questions 1) how pluripotent and adult stem cells maintain their unique cell states, and 2) how we can leverage their propensities for controlled differentiation for the creation of next-generation cell and tissue models. We utilize advanced genetic approaches to identify and interrogate regulatory machineries governing the stem cell state. This is coupled with the development of novel cell culture approaches to generate 3D cellular models that demonstrate higher-order structure and a greater repertoire of relevant cell types to closely mimic the in vivo cell niche. We are particularly interested in applying these techniques to understand etiologies of neurodegenerative and metabolic diseases. Our ultimate goal is to harness the power of stem cells to derive more physiological disease models that can drive novel therapeutic discoveries and eventually actualize the goal of personalized medicine.