The Perez White laboratory strives to conduct leading-edge research in the field of epidermal biology with the ultimate goal of impacting medicine and advancing our understanding of skin. To this end, we incorporate hypothesis-driven research with innovative disease models and discovery approaches. Specifically, we employ three-dimensional models of bioengineered reconstituted human epidermis and mouse models with proteomics, RNA-sequencing, or microarray analysis. We uniquely exploit our use of primary human cells to identify key signal transduction mechanisms that drive the physiological state and how these pathways may be hijacked to contribute to pathological states. The overall aim of our research direction is to define Eph receptor tyrosine kinase signal networks underlying epidermal homeostasis. As little is known about Eph receptors in skin biology, we performed a proteomics screen to generate a directory of EphA2-interacting proteins in primary human epidermal keratinocytes. So far, this rich resource has led us to appreciate an unrecognized role for EphA2 in tight junction morphogenesis. EphA2 promotes the de novo assembly and functional integrity of the epidermal tight junction barrier. The tight junction barrier is an indispensable structural network that prevents the movement of small molecules (water, solutes, ions, proteins, and pathogens, infectious agents, and allergens) into or out of an organism. Perturbations in tight junctions are relevant to several skin disorders such as cancer, atopic dermatitis, and psoriasis.