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:10113544
- 负责人:
- 金额:$ 15.92万
- 依托单位:
- 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:
- 关键词:AcneAcne VulgarisAffectAnaerobic BacteriaAntibioticsAwardBindingBiochemicalBiological ProcessBiologyChelating AgentsClinicalCommunitiesDairy ProductsDermatologyDiseaseDisease remissionDoctor of MedicineDoctor of PhilosophyEnvironmentExanthemaFacultyFoundationsFundingGenesGenomeGenomicsGoalsGrantGrowthHemeHemolysinHumanImmune systemImmunologyInfectionInfection preventionInflammationInflammatoryInstitutionInvestigationIronIsotretinoinLeukocyte L1 Antigen ComplexLightMass Spectrum AnalysisMedical ResearchMentorsMetabolicMetabolic PathwayMetabolismMetagenomicsMetal exposureMetalsMicrobeMicronutrientsNutritional ImmunityPathway interactionsPatientsPeptide HydrolasesPharmaceutical PreparationsPhototherapyPhysiciansPorphyrinsPositioning AttributePredispositionPropionibacteriumPropionibacterium acnesProteinsPublishingResearchResearch DesignResearch PersonnelResource DevelopmentRoleRunningSamplingScientistSecureSkinSkin colonizationStructureSunlightSwabSystemTechniquesTestingTrace metalTrainingTransition ElementsTranslational ResearchUnited StatesUnited States National Institutes of HealthUniversitiesVirulence FactorsVirulentWashingtonWood materialWorkbasecareercareer developmentchelationcommensal bacteriaconsumer productcostexperiencegene synthesisheme-binding proteinhigh schoolhuman pathogenhuman studyimprovedmedical schoolsmeetingsmetabolomicsmetal chelatormetal metabolismmicrobialmicroorganism growthnovelnovel therapeuticsoxidationpathogenpressurepsoriasinresponseskillsskin disorderskin microbiomeskin microbiotatenure tracktranscriptome sequencingwater 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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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William Howard McCoy IV其他文献
William Howard McCoy IV的其他文献
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{{ truncateString('William Howard McCoy IV', 18)}}的其他基金
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
- 批准号:
10359118 - 财政年份:2020
- 资助金额:
$ 15.92万 - 项目类别:
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
- 批准号:
10585915 - 财政年份:2020
- 资助金额:
$ 15.92万 - 项目类别:
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