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Microbial Shifts and Immune Dysregulation in Hidradenitis Suppurativa Pathogenesis

化脓性汗腺炎发病机制中的微生物变化和免疫失调

基本信息

批准号：
10190838
负责人：
Haley Naik
金额：
$ 17.75万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10190838
关键词：
16S ribosomal RNA sequencing Abscess Acne Address Affect Anaerobic Bacteria Antibiotic Therapy Biology CCL2 gene Cicatrix Clinic Clinical Trials Complex Cutaneous Data Data Set Dermatology Development Disease Drainage procedure Environment Flare Foundations Funding Future Gene Activation Gene Expression Gene Expression Profile Genes Genomics Goals Hidradenitis Suppurativa Human Human Microbiome Immune Immune System Diseases Immune response Immunology Inflammatory Inflammatory Response Interleukin-1 beta Interleukin-12 Interleukin-17 Interleukin-6 Intervention Intervention Studies Investigation K-Series Research Career Programs Knowledge Lesion Medical Mentors Metagenomics Methods Minority Morbidity - disease rate Nodule Pain Pathogenesis Pathogenicity Pathway interactions Patients Play Population Prevalence Process Property Regulation Research Research Design Role Sebaceous Glands Sebum Severity of illness Signal Transduction Site Skin Skin colonization Specimen Structure TNF gene Taxon Techniques Testing Therapeutic Therapeutic Intervention Training Training Programs Woman Work adalimumab antimicrobial base chronic inflammatory disease clinically relevant commensal bacteria cytokine design effective therapy experience functional genomics healthy volunteer immune activation immunoregulation microbial microbial colonization microbiota novel therapeutic intervention novel therapeutics response skin disorder skin lesion skin microbiome skin microbiota targeted agent targeted treatment therapeutic target transcriptome transcriptome sequencing transcriptomics translational medicine translational scientist young woman

项目摘要

PROJECT SUMMARY Hidradenitis suppurativa (HS) is a disabling chronic inflammatory disease with few effective treatments that affects 1-4% of the Western population, predominantly women (M:F 1:3) and minorities. Despite its prevalence and morbidity, HS pathogenesis is poorly understood and this has limited the development of effective therapies. Although abnormal microbial colonization and immune dysregulation have been implicated in HS pathogenesis, neither has been rigorously studied. To address this gap, Dr. Naik’s K23 proposal will use comprehensive, systematic, unbiased approaches to investigate skin microbial perturbations and dysregulated inflammatory responses in HS. Findings from these foundational studies will guide the identification of therapeutic targets and selection of available targeted treatments for testing in future R01 studies. Dr. Naik’s goal is to become an independent R01-funded clinic-based translational investigator leading pioneering research to test novel therapies for inflammatory skin diseases and applying mechanistic studies within the context of clinical trials to deepen our understanding of disease biology. She is seeking a K23 Career Development Award to pursue focused training in mechanistic studies in human skin microbiome and cutaneous immunology research, which will be essential to achieving this goal. She has assembled an exceptional mentoring team with expertise in translational medicine (Dr. David Wofsy), human microbiome (Dr. Heidi Kong and Dr. Susan Lynch), cutaneous immunology (Dr. Michael Rosenblum), and complex medical dermatology (Dr. Kanade Shinkai). Together with her mentoring team, she has developed a rigorous training program that includes outstanding mentoring, structured tutorials, didactic coursework, and practical experience. Through the proposed research aims, she will acquire in-depth training in the concrete steps of conducting mechanistic studies in human skin microbiome and cutaneous immunology research, including study design, specimen procurement and processing methods, and computational approaches in metagenomics and functional genomics. The following research aims have been designed to align with the mentoring and didactic training proposed in this application. The rationale for this proposed research is that characterizing C. acnes perturbations over HS disease course and activation of genes in the IL-17/IL-6 immune pathway in HS may elucidate pathogenic and targetable pathways for subsequent interventional investigations. This proposal will determine how and to what extent the relative abundance of C. acnes is perturbed at HS lesional sites and sites of HS predilection over disease course (Aim 1) and whether the IL-17/IL-6 axis is a dominant immune pathway in HS lesional skin as compared with non-lesional and HV skin (Aim 2). Accomplishing these aims will provide the preliminary data needed for a competitive R01 application to select and test novel therapeutic approaches for HS.

项目总结