The ultimate goal of our laboratory is to obtain a mechanistic understanding of the cellular and molecular basis of tissue regeneration and repair, and how to control these processes for therapeutic applications. A wide array of experimental approaches ranging from genetic engineering of mouse models to cell biology and biochemistry to quantitative biology is brought to bear in these investigations. This multidisciplinary approach is marshalled to gain a fundamental understanding of the regulation of tissue homeostasis, using the skin as an experimental platform. Within the skin, the epithelial compartment (the epidermis and hair follicle) is one of the few structures in the mammalian body that undergoes cyclic regeneration throughout the lifetime of the animal. Moreover, as the primary mode of protection from physical and chemical assaults, the epithelium is often damaged and has evolved an amazing capacity to rapidly repair itself. Current efforts are aimed at unraveling the complex crosstalk between the ensemble of cells that mediate the three phases of the wound-healing program: the inflammatory phase, proliferative phase, and remodelling phase. Within the context of this complex and multifactorial process, our research program has two major foci: 1) The investigation of the early cellular events that launch the wound-healing program and advance the cell state transition of epidermal keratinocytes from homeostasis to tissue repair; 2) The convergence of the extracellular matrix, vasculature, and inflammatory cells with dermal fibroblasts to stimulate scar formation and the pathological condition of over-scarring known as fibrosis. These studies provide an entry point into understanding the wide variety of diseases that exploit and deregulate these processes, which has led to the resurgence of the hypothesis of diseases with a “wound signature”. Consequently, though the research projects are firmly rooted in understanding the basic biology of skin homeostasis, regeneration and repair, they also have considerable potential to promote the development of novel therapeutics for a variety of common diseases. These translational applications, in turn, have provided opportunities to interface with the pharmaceutical and biotech industries.