Grant: Operating Grant: Industry-partnered Collaborative Research

Granzyme B (GzmB) is a protein-degrading enzyme that is induced by sunlight (UV). When GzmB is elevated in the skin, it prevents the skin from repairing itself and this can lead to scarring. Our previous work, in which we genetically knocked out GzmB, showed that we could improve tissue repair and visible signs of skin damage in mice that were exposed to repetitive solar-simulated UV light. In a related phenomenon, the autoimmune disease, Discoid Lupus Erythematosus (DLE), involves the formation of irreversible scar-like lesions that are triggered by sunlight. While normal skin has minimal GzmB, GzmB is highly abundant in both DLE skin lesions as well as in chronic, sun-exposed skin. Our research suggests inhibition of GzmB improves skin repair and prevents scarring. In collaboration with viDA Therapeutics Dr. Granville's laboratory has developed a novel, small molecule inhibitor of GzmB that can be applied topically to the skin. The proposed work will provide important proof of concept data that will be used as evidence to support the clinical use of a formulated GzmB inhibitor to reduce scarring in skin conditions such as DLE where this enzyme is believed to disrupt normal healing.