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Mechanistic Investigations of Sebaceous Skin Microbial Community Remodeling in Acne Remission

痤疮缓解中皮脂皮肤微生物群落重塑的机制研究

基本信息

批准号：
10585915
负责人：
William Howard McCoy IV
金额：
$ 15.92万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10585915
关键词：
Acne Acne Vulgaris Affect Anaerobic Bacteria Antibiotics Award Binding Biochemical Biological Process Biology Chelating Agents Clinical Communities Dairy Products Dermatology Disease Disease remission Doctor of Medicine Doctor of Philosophy Dryness Environment Exanthema Faculty Foundations Funding Genes Genome Genomics Goals Grant Growth Heme Hemolysin Human Immune system Immunology Infection Infection prevention Inflammation Inflammatory Institution Investigation Iron Isotretinoin Leukocyte L1 Antigen Complex Light Mass Spectrum Analysis Medical Research Mentors Metabolic Metabolic Pathway Metabolism Metagenomics Metal exposure Metals Microbe Micronutrients Modeling Nutritional Immunity Pathway interactions Patients Peptide Hydrolases Pharmaceutical Preparations Phototherapy Physicians Porphyrins Positioning Attribute Predisposition Propionibacterium Propionibacterium acnes Protein Secretion Proteins Publishing Research Research Design Research Personnel Resource Development Role Running Sampling Scientist Secure Skin Skin colonization Structure Sunlight Swab System Techniques Testing Trace metal Training Transition Elements Translational Research United States United States National Institutes of Health Universities Virulence Factors Virulent Washington Wood material Work career career development chelation commensal bacteria consumer product cost experience gene synthesis heme-binding protein high school human pathogen human study improved medical schools meetings metabolomics metal chelator metal metabolism microbial microorganism growth novel novel therapeutics oxidation pathogen pressure psoriasin response skills skin disorder skin microbiome skin microbiota tenure track transcriptome sequencing water conservation

项目摘要

PROJECT SUMMARY/ABSTRACT Wood’s lamp examination of any patient will reveal Cutibacterium acnes, the microbe associated with acne. This technique excites C. acnes porphyrins. It is not known how or why they are secreted, but they cause inflammation and can bind metals. Light therapy can excite porphyrins to kill C. acnes and temporarily improve acne. Isotretinoin is a non-antimicrobial acne treatment that increases healthy skin microbes and human proteins that limit metals. My K08 project will test the hypothesis that these proteins select for healthy skin microbes. We believe that our findings will lead to new therapies that cultivate (rather than kill) microbes to cure disease. Candidate. I have been training to be a physician scientist since my senior year of high school in 1997. During my M.D.-Ph.D., I studied immunology and used structure-function studies to dissect host-pathogen interactions. This training led me to dermatology where I can see the immune system at work in every rash. As a resident, I conducted a human study assessing how microbes change in acne remission. I published these findings and they now support my proposed K08 mechanistic studies. My career goal is to run a translational research lab that studies how interactions between humans and microbes impact skin disease. My K08 work will build the scientific foundation for this work and provide the skills that I need to transition to independence. Environment. With exceptional researchers, collegiality, and career development resources, Washington University School of Medicine (WUSM) is an ideal institution for a K08 award, where I will attend frequent scientific meetings, career development seminars, and didactics to prepare myself for a tenure-track position. My mentor (Dr. Jeffrey Henderson) is a world-expert in using mass spectrometry(MS)-based metabolomics to study human-microbe competition over metals. He has multiple NIH grants supporting these types of studies and has extensive expertise using MS and biochemical approaches to study metal and heme metabolism. WUSM is an exceptional place to pursue medical research and that is why I joined the WUSM faculty in 2017. Research. Human skin uses microbial, physical, and secreted barriers to prevent infection. Secreted proteins can limit metals, but their role in this system is unclear. It is also unclear how the normal skin microbe C. acnes acquires metals or why it secretes porphyrins, which can bind metals (e.g. heme) and cause inflammation. Light therapy activates porphyrins to kill C. acnes and temporarily improve acne. A non-antimicrobial drug (isotretinoin) can cure acne. It increases healthy skin microbes and human proteins that limit metals. I hypothesize that human proteins limit metals to select for healthy skin microbes. I will test this hypothesis by identifying C. acnes pathways enriched by isotretinoin and determining if C. acnes uses porphyrins or RoxP to acquire metals.

项目总结/文摘