As the body's primary environmental interface, the skin epidermis is routinely exposed to inflammatory pathogens and noxious agents. Epidermal stem cells (EpdSCs) maintain the epidermal barrier throughout an organism's lifetime. Despite EpdSCs' vulnerability to inflammation, we understand neither their primary response to nor the long-term effects of inflammation on these stem cells. Thus, for my postdoctoral studies, I am evaluating how inflammation impacts epidermal stem cells and its long-term consequences for tissue fitness and function. Building upon this theme, for my independent research phase, I propose in Aim 1 to evaluate the role of skin-resident ROR?t+ cells in directing EpdSC behavior during wound healing. The skin is also home to a constellation of commensal organisms and is thus replete with microbial stimuli. Although shifts in skin microbial communities are associated with chronic wounds, the factors controlling the wound microbiota and its downstream effects on wound repair are poorly understood. Thus, in Aim 2 I propose to dissect the role of ROR?t+ cells in modulating skin commensals and further examine the contribution of ?healthy? and ?wound? microbial communities to wound repair. Such an understanding will reveal novel functions for ROR?t+ cells in the modulation of EpdSC function and skin microbial communities when the skin barrier is breached. These studies will also identify novel molecular EpdSC-specific and microbial therapeutic targets for improved wound management.
Chronic or non-healing wounds affect approximately 2% of the U.S. population and cost an estimated 50 billion dollars to treat annually. Here I propose to examine the role of skin resident ROR?t+ immune cell populations in the control of wound repair to further our understanding of the cellular and molecular factors that underlie this complex process. My studies will uncover novel targets aimed at modulating ROR?t+ cells, epidermal stem cells, and/or the skin microbiota to advance diagnostic and therapeutic approaches in pathological tissue repair. !
