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

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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.