Our research is focused on understanding the contribution of environmental and genetic factors in the development of disease. The relative impact of these factors to pathogenesis is not well understood for many disorders. Complex interactions between genes and the environment have made it particularly difficult to develop accurate models for the sporadic and so called multifactorial forms of human disease. To further complicate studies, biopsied tissue containing the affected cell type is often extremely limited. Moreover, the developmental or pathological events leading to the disease have usually occurred long before diagnosis. While animal models exist for several diseases, they usually represent a rare, ‘single-hit’, genetic form of a disease that may not completely or accurately reflect the human disorder nor recapitulate the influence of environmental factors in the development of the pathological state. As a result, it has been extremely difficult to discern the contribution of either genetic or environmental factors in the development of the more common complex diseases, such as type-1 diabetes, Parkinsons and cardiovascular disease. To help overcome these technical difficulties and expand our understanding of these and other complex diseases we are building in vitro models using human embryonic stem cells, in which genetic and developmental aspects of the disease can be controlled.