Genetic disruption of skin development and differentiation is responsible for diseases that affect >20% of the population, underscoring the importance of this process to human health. We study the human skin in the laboratory and in the clinic. In the lab, we use primary skin cells, regenerated human epidermal tissue, and xenograft models to decipher the molecular pathways critical to epidermal development and homeostasis. In the clinic, we investigate the molecular pathogenesis of genetic skin diseases. Our goal is to integrate laboratory and patient-oriented approaches to gain insight to the form and function of skin in health and disease. Our epidermal model systems allow for rapid and combinatorial genetic manipulations in a primary cell and tissue context. Combined with genome engineering tools such as CRISPR/Cas9, this experimental system serves as a versatile genetic approach to study stem cell biology, tissue development, and cellular differentiation.