grant
Role of a gut microbiota metabolite indole lactate in myelin repair
Organization JOHNS HOPKINS UNIVERSITYLocation BALTIMORE, UNITED STATESPosted 8 Jul 2025Deadline 30 Apr 2030
NIHUS FederalResearch GrantFY20252,3,7,8-Tetrachlorodibenzo-p-dioxin ReceptorsAH ReceptorsATAC sequencingATAC-seqATACseqAdoptive TransferAffectAgeAgingAmericanAnimal ModelAnimal Models and Related StudiesAntiinflammatory EffectAreaAromatic Amino AcidsAryl Hydrocarbon ReceptorAssay for Transposase-Accessible Chromatin using sequencingAstrocytesAstrocytusAstrogliaBacteriaBiological MarkersBiscyclohexanone OxaldihydrazoneBloodBlood Reticuloendothelial SystemBlood SerumBody TissuesCD140a AntigensCNS DiseasesCNS disorderCausalityCell AgingCell BodyCell DifferentiationCell Differentiation processCell SenescenceCellsCellular AgingCellular SenescenceCentral Nervous System DiseasesCentral Nervous System DisordersChildhoodCirculationClinicalCuprizoneDataDegenerative Neurologic DisordersDemyelinationsDifferentiation in cell cultureDioxin ReceptorsDisablingDiseaseDisorderDisseminated SclerosisEAEEatingElectron MicroscopyEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEpithelial CellsEtiologyExperimental Allergic EncephalitisExperimental Allergic EncephalomyelitisExperimental Autoimmune EncephalitisExperimental Autoimmune EncephalomyelitisFermentationFoodFood IntakeFundingFutureGI microbiomeGI microbiotaGastrointestinal microbiotaGenomeGoalsGut EpitheliumHortega cellIn VitroIn vitro cell differentiationIndolesInflammationInflammatoryInjuryIntermediary MetabolismInvestigationKO miceKnock-outKnock-out MiceKnockoutKnockout MiceL-TryptophanLevotryptophanLinkLoxP-flanked alleleLysolecithinsLysophosphatidylcholinesMS patientMacrophageMeasuresMediatingMedulla SpinalisMetabolic PathwayMetabolic ProcessesMetabolismMiceMice MammalsMicrogliaMissionModelingMultiple SclerosisMurineMusMyelinMyelogenousMyeloidMyeloid CellsMφNINDSNational Institute of Neurological Diseases and StrokeNational Institute of Neurological Disorders and StrokeNeonatalNervous System Degenerative DiseasesNervous System DiseasesNervous System DisorderNeural Degenerative DiseasesNeural degenerative DisordersNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeurologic DisordersNeurological DisordersNeurosciences ResearchNuclear TranslocatorNull MouseOligodendrocytesOligodendrocytusOligodendrogliaOligodendroglia CellOralOutcome AssessmentPDGF alpha ReceptorPDGF receptor αPDGF-R-alphaPDGFR-αPDGFRαParticipantPathway interactionsPlatelet-Derived Growth Factor Receptor Alpha PolypeptidePlatelet-Derived Growth Factor alpha ReceptorPolyaromatic Hydrocarbon ReceptorsPropertyPublic HealthRNA SeqRNA sequencingRNAseqRelapsing-Remitting Multiple SclerosisReplicative SenescenceReportingResearchRiskRoleSamplingSerumSeverity of illnessSpinal CordStaining methodStainsSupplementationT-CellsT-LymphocyteTCDD ReceptorsTestingTherapeutic AgentsTissuesTryptophanYogurtadult youthage associated effectsage effectage related effectsagedaged miceaged mouseagesaging effectanti-inflammatory effectassay for transposase accessible chromatin followed by sequencingassay for transposase accessible chromatin seqassay for transposase accessible chromatin sequencingassay for transposase-accessible chromatin with sequencingastrocytic gliaautoimmune encephalomyelitisbacteria in the gutbio-markersbiologic markerbiomarkercausationcell typecellular differentiationcompare to controlcomparison controlcytokinedegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdemyelinatedesigndesigningdifferentiation in culturedifferentiation in vitrodigestive tract microbiomedisease causationdisease severityelderly miceenteric microbial communityenteric microbiomeenteric microbiotaepigeneticallyepigenomeexposomefloxedfloxed allelegastrointestinal epitheliumgastrointestinal microbial floragastrointestinal microbiomegitter cellglial activationglial cell activationgut bacteriagut communitygut floragut microbe communitygut microbial communitygut microbial compositiongut microbial consortiagut microbiomegut microbiotagut microbioticgut microfloragut-associated microbiomehESChuman ES cellhuman ESChuman embryonic stem cellimpact of agein vitro cellular differentiationin vivoinfluence of ageinjuriesinnovateinnovationinnovativeinsightinsular sclerosisintestinal biomeintestinal floraintestinal microbiomeintestinal microbiotaintestinal microfloraintestinal tract microfloramesogliametabolism measurementmetabolomemetabolomicsmetabonomemetabonomicsmicrobiota derived metabolitesmicrobiota metabolitesmicroglial cellmicrogliocytemodel of animalmultiomicsmultiple omicsmultiple sclerosis patientneural inflammationneurodegenerative illnessneuroinflammationneuroinflammatoryneurological diseasenew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyold miceoligodendrocyte differentiationoligodendrocyte precursoroligodendrocyte precursor celloligodendrocyte progenitoroligodendrocyte stem cellpanomicspathwaypatients with MSpatients with multiple sclerosispediatricpediatric multiple sclerosispediatric onset MSpediatric onset multiple sclerosispeople with Multiple sclerosisperivascular glial cellplatelet-derived growth factor receptor αre-myelinatere-myelinationremyelinateremyelinationrepairrepairedreplicative agingresearch studyscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolethymus derived lymphocytetooltranscriptome sequencingtranscriptomic sequencingtranslational neuroscienceyoung adultyoung adult ageyoung adulthood
Description preview
Project Summary
Multiple sclerosis (MS) is the most common neurodegenerative disease in young adults. Changes in the serum
metabolome have been reported in MS and our preliminary data demonstrate that they are also associated with
MS disease severity. We specifically show that aromatic amino acid-derived lactate metabolites, produced by
the gut…
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