Featured Publications
Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions
Chen H, Rosen C, González-Hernández J, Song D, Potempa J, Ring A, Palm N. Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions. Cell 2023, 186: 3095-3110.e19. PMID: 37321219, PMCID: PMC10330796, DOI: 10.1016/j.cell.2023.05.024.Peer-Reviewed Original ResearchCommensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 2022, 378: eabm3233. PMID: 36302024, PMCID: PMC9993714, DOI: 10.1126/science.abm3233.Peer-Reviewed Original ResearchConceptsColorectal cancerInflammatory bowel disease patientsBowel disease patientsInflammatory bowel diseaseIndigenous gut microbesBowel diseaseDisease patientsCommensal microbiotaDNA damageColon tumorigenesisElicit DNA damageGut microbesGenotoxic metabolitesGut commensalsMorganella morganiiPatientsGenotoxic chemicalsDiseaseMicrobiotaMetabolitesGenotoxicityCancerMiceFull spectrumDamageWithin-host evolution of a gut pathobiont facilitates liver translocation
Yang Y, Nguyen M, Khetrapal V, Sonnert ND, Martin AL, Chen H, Kriegel MA, Palm NW. Within-host evolution of a gut pathobiont facilitates liver translocation. Nature 2022, 607: 563-570. PMID: 35831502, PMCID: PMC9308686, DOI: 10.1038/s41586-022-04949-x.Peer-Reviewed Original ResearchConceptsHost evolutionGene expression programsCell wall structureNon-synonymous mutationsComparative genomicsIndependent lineagesExperimental evolutionExpression programsDivergent evolutionRegulatory genesBacterial behaviorCritical regulatorBacterial translocationGut commensalsTranslocationE. gallinarumMesenteric lymph nodesInitiation of inflammationImmune evasionWall structureEvade DetectionMucosal nicheLactobacillus reuteriCommensalGut microbiotaInterspecies commensal interactions have nonlinear impacts on host immunity
Rice TA, Bielecka AA, Nguyen MT, Rosen CE, Song D, Sonnert ND, Yang Y, Cao Y, Khetrapal V, Catanzaro JR, Martin AL, Rashed SA, Leopold SR, Hao L, Yu X, van Dijk D, Ring AM, Flavell RA, de Zoete MR, Palm NW. Interspecies commensal interactions have nonlinear impacts on host immunity. Cell Host & Microbe 2022, 30: 988-1002.e6. PMID: 35640610, PMCID: PMC9283318, DOI: 10.1016/j.chom.2022.05.004.Peer-Reviewed Original ResearchConceptsImmunological outcomesCell activationIntestinal epithelial cell activationInflammatory bowel disease patientsBowel disease patientsDendritic cell activationMesenteric lymph nodesSystemic antibody responsesEpithelial cell activationImmunological milieuLymph nodesAntibody responseDisease patientsAkkermansia muciniphilaGnotobiotic miceHost immunityCommensal microbesHuman cohortsHuman gut bacteriaGut bacteriaMiceAllobaculumMuciniphilaDiseaseIncomplete penetranceAutoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition
Chen JW, Rice TA, Bannock JM, Bielecka AA, Strauss JD, Catanzaro JR, Wang H, Menard LC, Anolik JH, Palm NW, Meffre E. Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition. Science 2020, 369: 320-325. PMID: 32675374, DOI: 10.1126/science.aay9733.Peer-Reviewed Original ResearchConceptsB cell toleranceB cellsCell toleranceEarly human fetal lifeHuman fetal B cellsPolyreactive B cellsHuman fetal lifeApoptotic cellsFetal B cellsHuman fetal liverB cell specificitySingle B cellsAbundant autoantibodiesGut microbiota assemblyNewborn seraFetal lifeBone marrowFetal developmentHealthy adultsCommensal bacteriaRepertoire breadthMicrobiota assemblyFetal liverPreimmune repertoireCell specificityA Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology
Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM, Palm NW. A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell 2019, 177: 1217-1231.e18. PMID: 31006530, PMCID: PMC6536006, DOI: 10.1016/j.cell.2019.03.036.Peer-Reviewed Original ResearchConceptsHost physiologyBioactive microbial metabolitesHuman gut bacteriaHost sensingProlific producersG proteinsGut microbiota metabolitesBlood-brain barrierL-PheMicrobial metabolitesOrphan GPCRsGut bacteriaColonic motilityInhibitor administrationMicrobiota metabolitesIntestinal microbiotaSmall moleculesDietary histidineBacteriaPhysiologyMicrobiota metabolomeMetabolitesGPR97Orthogonal approachGPCRsImmunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease
Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease. Cell 2014, 158: 1000-1010. PMID: 25171403, PMCID: PMC4174347, DOI: 10.1016/j.cell.2014.08.006.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseBowel diseaseIgA coatingIntestinal microbiotaIntestinal bacteriaGerm-free miceIBD patientsIntestinal diseaseImmunoglobulin AMouse modelDiseaseAnaerobic culturingDramatic susceptibilityTargeted eliminationDisease developmentDisease susceptibilityMiceCell sortingMicrobiotaBacterial cell sortingFecal bacteriaSuch bacteriaColitisPatientsIgA
2024
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Hamchand R, Wang K, Song D, Palm N, Crawford J. Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca. Nature Communications 2024, 15: 8902. PMID: 39406708, PMCID: PMC11480411, DOI: 10.1038/s41467-024-53185-6.Peer-Reviewed Original ResearchConceptsK. oxytocaGeneral carbohydrate metabolismVirulence factor productionPLP-dependent enzymesAssociated with gutEnterobactin biosynthesisAutoinducer signalBacterial virulenceKlebsiella oxytocaSpecific carbohydratesHost immune responseCarbohydrate metabolismAutoinducerMolecular signalsVirulenceHistamine receptor H4BiosynthesisHost signalAcquisition responsesProtease inhibitorsPathwayHostLung pathologyLung isolationImmune responseThe Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching
Lam Y, Hamchand R, Mucci N, Kauffman S, Dudkina N, Reagle E, Casanova-Torres Á, DeCuyper J, Chen H, Song D, Thomas M, Palm N, Goodrich-Blair H, Crawford J. The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching. Applied And Environmental Microbiology 2024, 90: e00528-24. PMID: 38916293, PMCID: PMC11267870, DOI: 10.1128/aem.00528-24.Peer-Reviewed Original ResearchRegulatory hierarchyG protein-coupled receptorsSmall molecule signalsHost-bacteria interactionsSymbiotic relationshipNatural productsHuman G protein-coupled receptorsAmino acid metabolismRegulating amino acid metabolismNull mutantsDiverse natural productsSecondary metabolismNematode progeny productionPathogen interactionsGlobal regulatorNematode egg hatchingWild typeInsect hostsSecondary metabolitesHatching rateLrhAAcylated appendagesMolecular networksMolecule signalsAmide signalsAn atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Hart T, Sonnert N, Tang X, Chaurasia R, Allen P, Hunt J, Read C, Johnson E, Arora G, Dai Y, Cui Y, Chuang Y, Yu Q, Rahman M, Mendes M, Rolandelli A, Singh P, Tripathi A, Ben Mamoun C, Caimano M, Radolf J, Lin Y, Fingerle V, Margos G, Pal U, Johnson R, Pedra J, Azad A, Salje J, Dimopoulos G, Vinetz J, Carlyon J, Palm N, Fikrig E, Ring A. An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms. Cell 2024, 187: 4113-4127.e13. PMID: 38876107, DOI: 10.1016/j.cell.2024.05.023.Peer-Reviewed Original ResearchCell invasionHost-microbe interactionsArthropod-borne pathogensHost sensingMicrobe interactionsTranscriptional regulationLyme disease spirocheteMicrobial interactionsExtracellular proteinsMicrobial pathogenesisEpidermal growth factorTissue colonizationEnvironmental cuesBacterial selectivityIntracellular pathogensPutative interactionsNext-generation therapeuticsPathogensFunctional investigationsInteractomeVector-borne diseasesImmune evasionPathogenic mechanismsStrainUnmet medical needA microbiota derived metabolite and pediatric celiac disease pathogenesis
Kelley K, Girdhar K, Dogru Y, Yang Y, Tolstikov V, Kiebish M, Palm N, Ludvigsson J, Soto G, Zhang M, Altindis E. A microbiota derived metabolite and pediatric celiac disease pathogenesis. The Journal Of Immunology 2024, 212: 0798_4966-0798_4966. DOI: 10.4049/jimmunol.212.supp.0798.4966.Peer-Reviewed Original ResearchCD progressorsCeliac diseaseLamina propriaVillous atrophyTaurodeoxycholic acidOverexpress IL-15HLA-DQ8 moleculesIncreased IgA responsesNatural killer cellsHLA-DQ8 allelesProspective cohort studyPathogenesis of CDC57BL/B6 micePlasma metabolomeCD4+T cellsKiller cellsT cellsCeliac disease pathogenesisIL-15Autoimmune conditionsHLA-DQ8HLA-DQ2Intraepithelial lymphocytesVilli/crypt ratioCohort studyA host–microbiota interactome reveals extensive transkingdom connectivity
Sonnert N, Rosen C, Ghazi A, Franzosa E, Duncan-Lowey B, González-Hernández J, Huck J, Yang Y, Dai Y, Rice T, Nguyen M, Song D, Cao Y, Martin A, Bielecka A, Fischer S, Guan C, Oh J, Huttenhower C, Ring A, Palm N. A host–microbiota interactome reveals extensive transkingdom connectivity. Nature 2024, 628: 171-179. PMID: 38509360, DOI: 10.1038/s41586-024-07162-0.Peer-Reviewed Original ResearchNiche colonizationHost–microorganism interactionsHost-microbiota interactionsInvade host tissuesStrain-specific interactionsHost cells in vitroConspecific strainsEffect of indigenous microorganismsHost biologyHost proteinsSecreted proteinsCommensal microorganismsExoproteinsBacterial strainsDiverse phylogenyMolecular basisMyriad microorganismsTissue of originTissue isolationCells in vitroInteractomeBinding patternsHost tissuesBiological logicHost immune system in vivo
2013
Bee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity
Palm NW, Rosenstein RK, Yu S, Schenten DD, Florsheim E, Medzhitov R. Bee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity. Immunity 2013, 39: 976-985. PMID: 24210353, PMCID: PMC3852615, DOI: 10.1016/j.immuni.2013.10.006.Peer-Reviewed Original ResearchMeSH KeywordsAnaphylaxisAnimalsBee VenomsCrotalid VenomsGenes, ReporterImmunity, InnateImmunoglobulin EImmunoglobulin GInsect ProteinsInterleukin-1 Receptor-Like 1 ProteinInterleukin-33Interleukin-4InterleukinsLymphocyte ActivationLysophospholipidsMelittenMembrane LipidsMiceMice, Inbred BALB CMice, KnockoutMyeloid Differentiation Factor 88OvalbuminPhospholipases A2PhospholipidsReceptors, IgEReceptors, InterleukinTh2 CellsConceptsInnate immune systemBee venom phospholipase A2Components of venomPhospholipase A2Immune responseGroup 2 Innate Lymphoid Cell ActivationVenom phospholipase A2Immune systemInnate lymphoid cell activationType 2 immune responsesLymphoid cell activationType 2 responsesProtective immune responseConfer protective immunityIgE responseInterleukin-33Receptor ST2Protective immunityCell type responsesCell activationLethal doseMajor allergenBee venomAllergensVenom toxins
2012
Allergic host defences
Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature 2012, 484: 465-472. PMID: 22538607, PMCID: PMC3596087, DOI: 10.1038/nature11047.Peer-Reviewed Original Research