Grant: Project Grant

The skin is our largest organ, and plays a critical role in protecting our bodies from infection and disease. Injury to the skin compromises this barrier function, increasing infection risk and its consequences, from organ failure, to limb loss, or death. It is vital that the skin undergoes an effective and rapid healing process. Disrupted skin wound repair can cause problems as bad as or worse than the initial injury. Excessive skin healing results in thickened scar tissue, which can be painful to the point of interfering with normal daily life. Incomplete healing results in an ulcer or open wound that compromises the skin barrier, leading to tissue loss, pain, limb amputation and death. Treatments to improve wound healing may reduce scarring or speed up wound closure, resulting in better and quicker healing. The main events in skin repair are well-defined - clotting, recruitment of immune cells to fight infection followed by production of cells within the injury to rebuild. Last, there is remodeling of the wound site that ideally leads to a perfectly healed, scar-free wound site. Developing new treatments requires a better understanding of these stages, including the key proteins involved. We have previously identified proteins that are critical for injury repair in the skin and heart. In the proposed studies, we will investigate the specific roles of these proteins in traumatic tissue damage to better understand wound healing mechanisms, and will examine how age and sex affect these processes. We will conduct unbiased searches for new regulators of injury repair. Finally, we will investigate how these target proteins and processes impact the healing of injuries related to cancer treatment: chemotherapy- and radiation-caused skin damage. These findings will define new options to treat skin wounds so that repair is faster, better quality and with less risk of scarring. Given the large global burden of skin injury, this work will have wide-ranging impact.