Abstract
Research in the Hardman group focuses on understanding multiple wound healing mechanisms to identify novel aspects of wound pathology. Here we will focus on two areas that hold great therapeutic opportunity. 1) Our studies have revealed a major role for estrogen as a pleiotropic regulator of wound repair. Post-menopause the ability to repair acute wounds rapidly decreases. We have made extensive use of the overiectomised murine model of human menopause to experimentally dissect the effects of estrogen on wound repair. More recently we have begun to dissect cutaneous estrogen signalling, revealing differential roles for the two estrogen receptors in healing. This work has now progressed to a Phase II clinical trial. 2) It has long been appreciated that the skin is colonised by a multitude of microorganisms, collectively termed the cutaneous microbiota. Recent technological advances have allowed detailed profiling of the diverse bacteria that inhabit our skin. Surprisingly, despite bacterial wound colonisation and infection being a major clinical concern, mechanistic understanding of host-microbiota interactions during skin wound healing remains poor. Using a combination of clinical and mouse mechanistic studies we provide new insight into the ability of skin bacteria to modulate wound repair. Moreover, we demonstrate that experimental manipulation of host pattern recognition receptors directly, and indirectly, alters healing outcome. Collectively, our findings provide substantial new insight into the importance of systemic hormones and host-microbiota interactions in modulating our skin’s ability to heal.