Grant: Operating Grant: Industry-partnered Collaborative Research

Granzyme B (GzmB) is an enzyme that has been found to accumulate in tissues and bodily in conditions associated with aging and inflammation and contributes to tissue deterioration and loss of function. GzmB is elevated in a number of skin disorders involving increased age and/or unresolved inflammation. Our data suggests that GzmB accumulation in the skin can not only cause further injury and inflammation, but can also impair the repair of damaged skin. It is estimated that up to 20-26% of patients in long-term care facilities suffer from chronic inflammation and impaired wound healing. Further, when wounds do actually heal in the elderly, the skin never regains its original strength and is therefore much more prone to further injury and skin tearing. Our evidence in several models suggests that inhibition of GzmB not only prevents tissue injury, but has the potential to prevent future re-injury as its inhibition in models of aging and impaired healing is associated with increased skin thickness and strength. The present grant seeks to capitalize on these discoveries to develop a topical treatment that will be tested in models of impaired wound healing and skin inflammation.