Role of the FAAH-OUT locus in cutaneous wound healing

研究综述 这项提案将研究一名69岁妇女的不寻常表型， 加速皮肤伤口愈合，疤痕最小。基因组测序显示， 表型是由脂肪酸醛水解酶下游约8kb的缺失引起的 FAAH（FAAH）基因导致长非编码RNA（lncRNA）基因FAAH OUT的丢失。 本提案的目标是了解FAAH OUT删除如何导致加速的 伤口愈合在美国，慢性伤口的年医疗负担超过25美元 10亿美元，并随着人口老龄化而继续上升。迫切需要改进 了解皮肤伤口愈合的生物学过程，并创新新的 治疗在第一个目标中，我们将研究来自研究对象的正常和受伤的皮肤组织 使用空间转录组学、原位杂交和异种移植皮肤修复模型来了解 FAAH OUT基因座如何调节伤口愈合。在第二个目标中，我们将阐明FAAH OUT基因相互作用组，以深入了解其分子机制。通过研究一种罕见的 等位基因的个体具有显著增强的伤口愈合，该建议旨在产生 新的见解lncRNA在伤口修复中的作用，并发现新的人类验证的目标， 治疗皮肤伤口。

RESEARCH SUMMARY The proposal will study the unusual phenotype of a 69-year-old woman who displays exceptionally accelerated skin wound healing with minimal scarring. Genome sequencing revealed that her phenotype is caused by an ~8 kb deletion downstream of the fatty acid aldehyde hydrolase (FAAH) gene that results in the loss of a long noncoding RNA (lncRNA) gene named FAAH OUT. The goal of this proposal is to understand how the FAAH OUT deletion results in accelerated wound healing. In the United States, the annual medical burden of chronic wounds exceeds $25 billion and continues to rise with the aging population. There is a critical need to improve understanding of the biological processes underlying skin wound healing and to innovate new therapies. In the first aim, we will study normal and wounded skin tissue from the study subject using spatial transcriptomics, in situ hybridization, and xenograft skin repair models to understand how the FAAH OUT locus regulates wound healing. In the second aim, we will elucidate the FAAH OUT genetic interactome to gain insight to its molecular mechanisms. By studying a rare genetic allele of an individual with markedly enhanced wound healing, this proposal aims to generate novel insight to the role of lncRNAs in wound repair and discover new human-validated targets to treat cutaneous wounds.