Converting wound scar into healing with regeneration

About This Grant

Summary The goal of this grant is to understand the regulation of SHH-driven hair follicle neogenesis (HFN) in adult wounds. While much research focuses on wound healing, scarring, particularly from burns, trauma, and surgeries, remains largely overlooked. Scarring affects over 50% of the U.S. population, with 50 to 80 million new scars formed annually, resulting in significant cosmetic, psychological, and social burdens. Yet, no effective anti-scarring therapy currently exists. We previously developed a model in which large wounds in mice can lead to efficient hair follicle regeneration, opening the door to understanding the molecular mechanisms of HFN. Our lab has identified Sonic Hedgehog (SHH) as a critical factor in determining whether wounds heal with hair follicle regeneration or fibrosis and how SHH interacts with WNT and BMP signaling pathways for successful HFN. These findings raise new possibilities about the roles of SHH in the unresolved issue of wound scar remodeling: Can SHH remodel existing scars? If so, how long after wounding is it effective? And can this approach be applied to human scars? Furthermore, a longstanding question is how a developmental signal like SHH can be induced after wounding and what prerequisites are necessary for this signal to occur. This project aims to investigate the effect of SHH on old scars long after healing (Aim1), explore one of the upstream mechanisms we’ve identified as essential for SHH induction in large wounds (e.g., angiogenesis) (Aim 2), and examine how SHH signaling can similarly induce HFN using human fibroblasts (Aim 3).