P50AR080594

Acne: A Disease of Lipid Metabolism, Microbiome, and the Immune Response - Abstract / Project Summary

Overall, the 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. The aim is 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), which is the initial site where acne lesions develop. It is considered to be one of the key contributing factors in the pathogenesis of acne. The UCLA/UCSD research project is based on recent findings using transcriptomics, metagenomics, and lipidomics. These findings establish the goal of linking together these diverse biological responses into a model that may explain the pathogenesis of acne.

The UCLA/UCSD research project, titled "Acne: A Disease of Lipid Metabolism, Microbiome, and the Immune Response" and led by Modlin and Gallo, will initially focus on studying the role of TREM2 macrophages and adipogenic fibroblasts in the pathogenesis of acne. Preliminary data from single-cell RNA sequencing (scRNA-seq) and spatial-sequencing have identified these two cell populations as over-represented in acne lesions. The gene programs expressed by these cells reflect their link to altered lipid metabolism.

The project investigators will obtain acne biopsy specimens from Hata and Kim. They will then address the link between the immune response in acne lesions and the microbiome and lipid metabolism. The research project will be supported by a UCLA Bioinformatics Core (Pellegrini, Yang) to analyze scRNA-seq and spatial-sequencing data of acne lesions. A UCSD Microbiology and Metagenomics Core (Gallo, O'Neill) will isolate and characterize C. acnes strains, while lipidomics analysis (Bensinger, UCLA) will be performed on 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 through research seminars, an enrichment program, and advisory board meetings. Additionally, a pilot and feasibility project program will extend the research base. The resources and environment at UCLA/UCSD, including core facilities and the UCLA and UCSD Clinical and Translational Science Awards (CTSA) program centers, will be utilized. Furthermore, mentoring programs for medical and graduate students, postdoctoral fellows, dermatology trainees, and junior faculty will be incorporated.

The proposed studies will provide new insights into how lipid metabolism and the skin microbiome shape cutaneous immune responses, contributing to inflammation. This research has the potential for intervention in skin disease.

Los Angeles University Of California

NOT APPLICABLE

93.846 - Arthritis, Musculoskeletal and Skin Diseases Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

Los Angeles, California 900958348 United States

Single Zip Code

NIAMS Centers of Research Translation (CORT) (P50 - Clinical Trial Not Allowed) (RFA-AR-22-001)

Amendment Since initial award the total obligations have increased 387% from $1,568,723 to $7,641,573.