Role of the FAAH-OUT locus in cutaneous wound healing

FAAH-OUT 基因座在皮肤伤口愈合中的作用

基本信息

批准号：
10334272
负责人：
Bryan Sun
金额：
$ 50.66万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10334272
关键词：
Acute Aldehydes Alleles Binding Biological Assay Biological Process Cells Chromatin Cicatrix Clinical DNA Dermatology Enhancers Epithelial Fatty Acids Fibroblasts Foundations Genes Genetic Genetic Transcription Genetic study Genome engineering Genotype Goals Grant Human Hydrolase In Situ Hybridization Individual Injury Knockout Mice Laboratories Lead Learning Link Lipids Medical Messenger RNA MicroRNAs Modeling Molecular Molecular Conformation Molecular Genetics Mutagenesis Names Organoids Outcome Pathway interactions Patients Phenotype Physicians Process Property Proteins Regulatory Element Research Research Personnel Role Skin Skin Tissue Skin injury Skin repair Skin wound healing Study Subject Testing Tissues United States Untranslated RNA Woman Wound healing therapy aging population base chronic wound experience experimental study gain of function genome sequencing genomic locus improved innovation insight keratinocyte loss of function migration new therapeutic target novel novel therapeutics repair model skin regeneration skin wound skin xenograft targeted treatment tissue repair transcriptomics wound wound healing wound treatment

项目摘要

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.

研究摘要该提案将研究一个69岁妇女的异常表型，该表型异常显示通过最小的疤痕加速皮肤伤口愈合。基因组测序表明她表型是由脂肪酸醛水解酶下游的约8 kb缺失引起的（FAAH）基因会导致丢失长的非编码RNA（lncRNA）基因，名为FAAH。该提案的目的是了解FAAH删除如何导致加速伤口愈合。在美国，慢性伤口的年度医疗负担超过25美元十亿，随着人口老龄化的速度继续增长。有迫切需要改进了解皮肤伤口愈合并创新新的生物学过程疗法。在第一个目标中，我们将研究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如何调节伤口愈合。在第二个目标中，我们将阐明法庭消除遗传相互作用组，以了解其分子机制。通过研究罕见的遗传该建议旨在产生伤口愈合的人的等位基因明显增强对LNCRNA在伤口修复中的作用的新见解，并发现新的人类验证靶标治疗皮肤伤口。