2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2023
Increasing sensitivity of antibody-antigen interactions using photo-cross-linking
de la Peña A, Sewall L, de Paiva Froes Rocha R, Jackson A, Pratap P, Bangaru S, Cottrell C, Mohanty S, Shaw A, Ward A. Increasing sensitivity of antibody-antigen interactions using photo-cross-linking. Cell Reports Methods 2023, 3: 100509. PMID: 37426749, PMCID: PMC10326447, DOI: 10.1016/j.crmeth.2023.100509.Peer-Reviewed Original ResearchConceptsPolyclonal immune responseImmune responseTime pointsRational vaccine designLater time pointsEarly time pointsVaccine immunogensAnimal modelsAntibody detectionVaccine designIntermediate antibodiesEarly timepointsLater timepointsAntibodiesViral glycoproteinsTimepointsDifferent viral glycoproteinsSensitivity of detectionAntibody-antigen interactionsResponsePatientsVaccination
2022
No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Lu-Culligan A, Tabachnikova A, Pérez-Then E, Tokuyama M, Lee HJ, Lucas C, Monteiro V, Miric M, Brache V, Cochon L, Muenker MC, Mohanty S, Huang J, Kang I, Dela Cruz C, Farhadian S, Campbell M, Yildirim I, Shaw AC, Ma S, Vermund SH, Ko AI, Omer SB, Iwasaki A. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination. PLOS Biology 2022, 20: e3001506. PMID: 35609110, PMCID: PMC9129011, DOI: 10.1371/journal.pbio.3001506.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccinationMRNA vaccinationEarly pregnancyFetal sizeCoronavirus disease 2019 (COVID-19) mRNA vaccinationSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Maternal antibody statusAdverse neonatal outcomesSyndrome coronavirus 2Birth defectsPolyinosinic-polycytidylic acidCrown-rump lengthGross birth defectsUnvaccinated adultsMaternal illnessNeonatal outcomesVaccinated adultsAntibody statusTLR3 agonistEarly immunizationMurine pregnancyAntibody inductionCoronavirus 2Combining Cellular Immunology With RNAseq to Identify Novel Chlamydia T-Cell Subset Signatures
Johnson RM, Asashima H, Mohanty S, Shaw AC. Combining Cellular Immunology With RNAseq to Identify Novel Chlamydia T-Cell Subset Signatures. The Journal Of Infectious Diseases 2022, 225: 2033-2042. PMID: 35172331, PMCID: PMC9159333, DOI: 10.1093/infdis/jiac051.Peer-Reviewed Original ResearchConceptsProtective T cell clonesAntibacterial effector mechanismsT cells residentB cell helpT cell clonesCytokine polarizationImmune miceIL-10Protective immunityVaccine trialsIL-13Surrogate biomarkerEffector mechanismsGenital tractT cellsVaccine candidatesChlamydia trachomatisCells residentHelper functionCellular immunologyMouse studiesHuman investigationsReproductive tractGranzyme A.Investigational data
2016
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
2015
Paradoxical changes in innate immunity in aging: recent progress and new directions
Montgomery RR, Shaw AC. Paradoxical changes in innate immunity in aging: recent progress and new directions. Journal Of Leukocyte Biology 2015, 98: 937-943. PMID: 26188078, PMCID: PMC4661037, DOI: 10.1189/jlb.5mr0315-104r.Peer-Reviewed Original ResearchConceptsImmune responseInnate immune changesInnate immune responseCytokine levelsInappropriate elevationImmune changesNaïve cell populationT cellsAdaptive immunityViral infectionParadoxical increaseInnate immunityMultiple cell typesParadoxical changesCell populationsActivation stateImmunityCell typesSevere consequencesResponseTissue contextImmunosenescenceVaccinationPopulationInfection
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role
2013
Age-dependent dysregulation of innate immunity
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nature Reviews Immunology 2013, 13: 875-887. PMID: 24157572, PMCID: PMC4096436, DOI: 10.1038/nri3547.Peer-Reviewed Original ResearchConceptsMetabolic syndromeIntracellular killingInnate immunityToll-like receptor functionNeutrophil extracellular trap formationBasal cytokine productionInnate immune dysregulationDendritic cell populationsMonocyte-derived DCsChronic viral infectionsMyeloid cells-1Pro-inflammatory milieuChronic inflammatory conditionsInnate immune activationVirus-infected macrophagesExtracellular trap formationAge-dependent dysregulationInnate immune systemPattern recognition receptorsAge-associated alterationsMacrophage colony-stimulating factorGranulocyte/macrophage colony-stimulating factorColony-stimulating factorTLR expressionImmune dysregulation
2008
Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3β
Mohanty S, Town T, Yagi T, Scheidig C, Kwan KY, Allore HG, Flavell RA, Shaw AC. Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3β. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 5063-5068. PMID: 18367668, PMCID: PMC2278186, DOI: 10.1073/pnas.0801235105.Peer-Reviewed Original ResearchConceptsMurine embryonic fibroblastsDNA damageDependent substrate phosphorylationDNA double-strand breaksType IA topoisomerasesCell cycle checkpointsDNA-damaging agentsS cell cycle checkpointDouble-strand breaksRegulation of totalSubstrate phosphorylationGenomic stabilityDsDNA breaksDNA replicationCycle checkpointsHomologous recombinationDNA repairUnanticipated roleEmbryonic fibroblastsAtaxia telangiectasiaCellular responsesTopoisomerase 3βPhosphorylationRad3Important roleDefective signal transduction in B lymphocytes lacking presenilin proteins
Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, Xavier RJ, Shaw AC. Defective signal transduction in B lymphocytes lacking presenilin proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 979-984. PMID: 18195359, PMCID: PMC2242696, DOI: 10.1073/pnas.0707755105.Peer-Reviewed Original ResearchConceptsPresenilin proteinsDiverse cellular processesMultiple genomic datasetsPS proteinsSignal transduction eventsWhole-genome datasetsDefective signal transductionNotch family membersCalcium-dependent signalingCellular processesProtein substratesSignal transductionTransduction eventsProtein interactionsPS2 functionUnanticipated roleConditional alleleGenomic datasetsToll-like receptor signalingPathway analysisIntegrative analysisPosttranslational cleavageReceptor signalingRecombinase expressionProtein
1999
Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras
Shaw A, Swat W, Davidson L, Alt F. Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 2239-2243. PMID: 10051625, PMCID: PMC26767, DOI: 10.1073/pnas.96.5.2239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlastocystB-LymphocytesCell DifferentiationDNA-Binding ProteinsEmbryo, MammalianGene Rearrangement, B-Lymphocyte, Light ChainGenes, ImmunoglobulinImmunoglobulin Heavy ChainsImmunoglobulin kappa-ChainsImmunoglobulin Light ChainsImmunoglobulin Variable RegionKidneyMiceMolecular Sequence DataRas ProteinsRecombinant Fusion ProteinsSignal TransductionSpleenStem CellsTransfectionConceptsRas expressionVariable region gene assemblyEmbryonic stem cellsIg light chain gene rearrangementGene rearrangementsB cell developmentWild-type B cellsB lineage cellsLight chain gene rearrangementsDevelopmental checkpointsHeavy chain geneGene productsGene assemblyExpression constructsB cell differentiationGene expressionBlastocyst complementationIg heavy chain genesCell developmentCell differentiationVariable region genesB cellsDifferentiation potentialLineage cellsChain geneActivated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes
Shaw A, Swat W, Ferrini R, Davidson L, Alt F. Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes. Journal Of Experimental Medicine 1999, 189: 123-129. PMID: 9874569, PMCID: PMC1887686, DOI: 10.1084/jem.189.1.123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell DifferentiationCell SurvivalDNA-Binding ProteinsEnzyme ActivationGene Expression Regulation, DevelopmentalGenes, RAG-1Immunoglobulin Heavy ChainsImmunoglobulin kappa-ChainsMiceMice, KnockoutPhenotypeRas ProteinsRNA, MessengerStem CellsTranscription, GeneticUp-RegulationConceptsB cellsRAG-deficient backgroundPeripheral lymphoid tissuesB-cell lineageEarly B cell developmentB lineage cellsLymphoid tissueBcl-2 transgeneCD43 expressionRecombination-activating gene 1B cell developmentHeavy chain transgeneSurface markersB cell stageLineage cellsIntracellular pathwaysMature B-cell stageDeficient backgroundProgressionGene 1Survival signalsCell developmentOverall phenotypeResult of expressionCell lineages
1991
Cytoplasmic tail deletion converts membrane immunoglobulin to a phosphatidylinositol-linked form lacking signaling and efficient antigen internalization functions
Mitchell RN, Shaw AC, Weaver YK, Leder P, Abbas AK. Cytoplasmic tail deletion converts membrane immunoglobulin to a phosphatidylinositol-linked form lacking signaling and efficient antigen internalization functions. Journal Of Biological Chemistry 1991, 266: 8856-8860. PMID: 2026599, DOI: 10.1016/s0021-9258(18)31524-2.Peer-Reviewed Original ResearchConceptsPhosphatidylinositol-linked formSignal transduction functionsPhosphatidylinositol-linked proteinsB cell lymphoma A20Cytoplasmic domainCytoplasmic tailMembrane proteinsSignal transductionTransmembrane proteinTransmembrane residuesTransduction functionMolecular massInternalization functionProteinAntigen receptorAntigen presentationEarly eventsMembrane immunoglobulinIg moleculesMode of expressionTransductionMIgMB lymphocytesSignalingResidues
1990
Mutations of immunoglobulin transmembrane and cytoplasmic domains: Effects on intracellular signaling and antigen presentation
Shaw A, Mitchell R, Weaver Y, Campos-Torres J, Abbas A, Leder P. Mutations of immunoglobulin transmembrane and cytoplasmic domains: Effects on intracellular signaling and antigen presentation. Cell 1990, 63: 381-392. PMID: 2119890, DOI: 10.1016/0092-8674(90)90171-a.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibody FormationAntigensBase SequenceB-LymphocytesCalciumCell LineCell MembraneCytoplasmHumansImmunoglobulin mu-ChainsKineticsMiceMolecular Sequence DataMutagenesis, Site-DirectedOligonucleotide ProbesReceptors, Antigen, B-CellSequence Homology, Nucleic AcidSignal TransductionTransfectionConceptsCytoplasmic domainSignal transductionShort cytoplasmic domainDifferent protein interactionsMembrane-bound formMu chain geneProtein interactionsTransmembrane residuesIntracellular signalingChain geneSpecific mutationsTransductionAntigen presentationAntigen-specific receptorsMutationsTransmembraneB cellsGenesSignalingDomainResiduesCellsAssaysReceptors
1988
A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice
Nussenzweig M, Schmidt E, Shaw A, Sinn E, Campos-Torres J, Mathey-Prevot B, Pattengale P, Leder P. A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice. Nature 1988, 336: 446-450. PMID: 3143076, DOI: 10.1038/336446a0.Peer-Reviewed Original ResearchMeSH KeywordsAbelson murine leukemia virusAnimalsB-LymphocytesBone MarrowCell Transformation, NeoplasticCell Transformation, ViralEnhancer Elements, GeneticGenes, ImmunoglobulinHematopoietic Stem CellsHumansImmunoglobulin mu-ChainsLymphomaMiceMice, TransgenicPhenotypeProto-Oncogene ProteinsProto-Oncogene Proteins c-mycProto-OncogenesRNA, MessengerAllelic exclusion in transgenic mice carrying mutant human IgM genes.
Nussenzweig MC, Shaw AC, Sinn E, Campos-Torres J, Leder P. Allelic exclusion in transgenic mice carrying mutant human IgM genes. Journal Of Experimental Medicine 1988, 167: 1969-1974. PMID: 3133444, PMCID: PMC2189689, DOI: 10.1084/jem.167.6.1969.Peer-Reviewed Original ResearchConceptsAllelic exclusionHeavy chain geneChain geneMu chainsHuman mu chainsPrimary B cellsHybrid animalsIg heavy chain genesHuman heavy chainsMu expressionTransgenic mice resultsIgM geneGenesSimultaneous expressionSecreted versionTransgeneIg transgenesHeavy chainMice resultsTransgenic miceExpressionHuman Ig transgenesB cellsCellsVivo
1987
Allelic Exclusion in Transgenic Mice That Express the Membrane form of Immunoglobulin μ
Nussenzweig M, Shaw A, Sinn E, Danner D, Holmes K, Morse H, Leder P. Allelic Exclusion in Transgenic Mice That Express the Membrane form of Immunoglobulin μ. Science 1987, 236: 816-819. PMID: 3107126, DOI: 10.1126/science.3107126.Peer-Reviewed Original ResearchConceptsMembrane-bound formAllelic exclusionMembrane-bound proteinsMu chainsMu chain geneHeavy chainHeavy chain allelesHuman genesTransgenic miceImmunoglobulin μMessenger RNAMembrane formChain geneAntibody genesB cellsGenesImmunoglobulin M heavy chainHuman mu chainsMouse systemCellsRegulationMolecular formsRNATransgeneProtein