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