Acne: a disease of lipid metabolism, microbiome and the immune response

痤疮：一种脂质代谢、微生物组和免疫反应疾病

• 批准号: 10404436
• 负责人: Richard L Gallo
• 金额: $ 156.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10404436
• 关键词: Acne; Address; Architecture; Bacteria; Bioinformatics; Biological; Biopsy Specimen; Cells; Clinical and Translational Science Awards; Communities; Core Facility; Cutaneous; Data; Dermal; Dermatology; Development; Disease; Disease model; Environment; Faculty; Feasibility Studies; Fibroblasts; Fostering; Generations; Genes; Goals; Homeostasis; Human; Immune response; Immunology; In Vitro; Inflammation; Inflammatory; Institution; Intervention; Lesion; Link; Lipids; Maps; Medical Students; Mentors; Metagenomics; Microbe; Microbiology; Modeling; Molecular; Mus; Outcomes Research; Pathogenesis; Patients; Physicians; Pilot Projects; Population; Postdoctoral Fellow; Production; Public Health; Reactive Oxygen Species; Research; Research Personnel; Research Project Grants; Research Support; Resources; Role; Scientist; Sebum; Shapes; Site; Skin; Squalene; TREM2 gene; Testing; Time; Translational Research; Yang; adipokines; base; cathelicidin; cell type; design; genetic signature; graduate student; innovation; innovative technologies; insight; lipid metabolism; lipidomics; macrophage; meetings; member; microbial; microbial genomics; microbiome; microbiota; multidisciplinary; network models; novel therapeutic intervention; programs; response; single-cell RNA sequencing; skin disorder; skin microbiome; stem cells; transcriptomics

ABSTRACT / PROJECT SUMMARY Overall The overall goal of the UCLA/UCSD Acne Center for Research Translation (Acne CORT) is to bring together scientists with expertise in different aspects of microbiology, lipid metabolism and immunology to engage in translational research to study the interaction between the microbiota, lipid metabolism and the host immune response in acne. Cutibacterium acnes is the dominant bacterium of the pilosebaceous unit (PSebU), the initial site where acne lesions develop, and is considered to be one of the key contributing factors in the pathogenesis of acne. The UCLA/UCSD Research Project is based on our recent findings using transcriptomics, metagenomics and lipidomics, establishing the goal to link together these diverse biologic responses into a model that may explain the pathogenesis of acne. The UCLA/UCSD Research Project (Modlin, Gallo), “Acne: a disease of lipid metabolism, microbiome and the immune response”, will initially focus studies on the role of TREM2 macrophages and adipogenic fibroblasts in the pathogenesis of acne. Our preliminary data using from single cell RNA-sequencing (scRNA-seq) and spatial-sequencing identified these two cell populations as over-represented in acne lesions, with gene programs reflecting their link to altered lipid metabolism. The project investigators will obtain acne biopsy specimens (Hata, Kim), then address the link between the immune response in acne lesions to the microbiome and lipid metabolism. The Research Project will be supported by a UCLA Bioinformatics Core (Pellegrini, Yang) to analyze scRNA-seq and spatial-seq of acne lesions, a UCSD Microbiology and Metagenomics Core (Gallo, O'Neill) to isolate and characterize C. acnes strains, and lipidomics analysis (Bensinger, UCLA) of biopsy specimens and key cell types derived in vitro. Ultimately, the Bioinformatics Core will use mergeomics to combine data from transcriptomics, metagenomics and lipidomics to create a network model of the pathogenesis of acne. The Administrative Core will facilitate research interactions between the projects with: i) research seminars, an Enrichment Program and Advisory Board meeting; ii) a Pilot and Feasibility Project Program to extend the research base; and, iii) plans to utilize the resources and environment at UCLA/UCSD including core facilities, the UCLA and UCSD Clinical and Translational Science Awards (CTSA) Program Centers as well as the mentoring programs for medical and graduate students, postdoctoral fellows, dermatology trainees and junior faculty. The proposed studies will provide new insights into how lipid metabolism and the skin microbiome shape cutaneous immune responses contributing to inflammation, with the potential for intervention in skin disease.

摘要/项目总结 整体 UCLA/UCSD痤疮研究翻译中心（Acne CORT）的总体目标是汇集 具有微生物学、脂质代谢和免疫学不同方面专长的科学家， 转化研究，研究微生物群，脂质代谢和宿主免疫之间的相互作用 痤疮的反应。痤疮皮肤杆菌是毛囊皮脂腺单位（PSebU）的优势细菌， 痤疮病变发展的部位，并且被认为是痤疮发病的关键因素之一。 痤疮的发病机制。UCLA/UCSD研究项目基于我们最近的研究结果， 转录组学、宏基因组学和脂质组学，建立了将这些不同的生物学联系在一起的目标。 反应到一个模型，可以解释痤疮的发病机制。UCLA/UCSD研究项目 （Modlin，Gallo），“痤疮：脂质代谢，微生物组和免疫反应的疾病”，最初将重点关注 TREM 2巨噬细胞和成脂成纤维细胞在痤疮发病机制中的作用的研究。我们 使用来自单细胞RNA测序（scRNA-seq）和空间测序的初步数据鉴定了这些 两种细胞群在痤疮病变中过度表达，基因程序反映了它们与脂质改变的联系 新陈代谢.项目调查人员将获得痤疮活检标本（Hata，Kim），然后处理链接 痤疮病变对微生物组的免疫反应与脂质代谢之间的关系。该研究项目 将由加州大学洛杉矶分校生物信息学核心（Pellegrini，Yang）支持，分析scRNA-seq和空间-seq， 痤疮病变，UCSD微生物学和宏基因组学核心（Gallo，奥尼尔）分离和表征C. 痤疮菌株，以及活检标本的脂质组学分析（Bensinger，UCLA）和痤疮中来源的关键细胞类型。 体外最终，生物信息学核心将使用mergeomics来联合收割机从转录组学获得的数据， 宏基因组学和脂质组学来创建痤疮发病机制的网络模型。行政核心 将通过以下方式促进项目之间的研究互动：i）研究研讨会， 和咨询委员会会议; ii）试点和可行性项目计划，以扩大研究基础;以及iii） 计划利用UCLA/UCSD的资源和环境，包括核心设施、UCLA和UCSD 临床和转化科学奖（CTSA）项目中心以及以下项目的指导计划 医学和研究生，博士后研究员，皮肤科实习生和初级教师。拟议 研究将为脂质代谢和皮肤微生物组如何塑造皮肤免疫提供新的见解， 这些反应有助于炎症，具有干预皮肤病的潜力。