Our epithelial tissues form barriers that separate us from the outside world. As such they are subject to a barrage of external assaults, including pathogens, allergens, wounds and carcinogens. To cope with these stresses, these tissues must constantly be rejuvenated. They do so through resident stem cells, which have the ability to self-renew long term and differentiate to make and maintain the barrier tissue. These stem cells must also be able to sense and respond quickly to injury in order to fuel rapid tissue regeneration. How stem cells balance self-renewal and differentiation is of fundamental importance to our understanding of normal tissue maintenance and wound repair. The regulatory circuitry governing this normal balancing act must be intricately regulated in normal homeostasis, and then transiently altered to cope with injury responses. Increasing evidence suggests that the mechanism goes awry in inflammation and becomes hijacked in cancers.
Skin epithelium is an excellent model system to understand how stem cells remain quiescent during times of minimal wear and tear, how these cells become mobilized during active tissue regeneration and wound-repair, and how the normal process of stem cell activation goes awry in cancer and inflammation. We’ve identified and characterized at a molecular level the skin’s stem cells and shown that they reside in distinct niches that impart to the stem cells their behavior both in task and in the molecular properties they display. We use high throughput genetic and genomic approaches to dissect at a molecular level how stem cell interactions with their niches differ in homeostasis, wound repair and inflammation, and how heterogeneity in the tumor microenvironment can confer to stem cells resistance to chemo and immune therapies. Our global objective is to apply our knowledge of the basic science of epithelial stem cells to unfold new avenues for therapeutics.