Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Burns are responsible for an estimated 300,000 deaths per year worldwide, with approximately 11 million cases requiring medical attention. One of the negative consequences of thermal injuries is aberrant wound healing, such as keloids. Treatment and prevention of keloids is one of the greatest unmet challenges in burns, with no curative strategies at this time. Recent studies link local glucose and glucose transporter levels with wound healing. Specifically, lack of glucose transporter 1 (GLUT1) impairs healing of wounds or UV-damaged skin. Conversely, lack of GLUT1 decreases inflammation and excessive tissue production in psoriasis. Therefore, local glucose levels and GLUT1 expression have an integral role in the balance between impaired and excessive healing in conditions like keloids. Elevated generalized glucose levels and inflammation are consequences of increased metabolism seen in burns. One of mediators involved in this increased metabolism are mitochondrial uncoupling proteins. Uncoupling protein 2 (UCP2), which is at many sites including skin, increases GLUT1 expression and facilitates glucose uptake. UCP2 also activates a mediator of inflammation, NLRP3 inflammasome, which is elevated in burns. We propose that UCP2 expression is increased in burn skin and has role in normal and aberrant wound healing, likely through NLRP3 and GLUT1 expression. Ultimately, persistent alterations in inflammation and local glucose levels could detrimentally affect wound healing, predisposing patients to keloids.