2020
Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults
Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults. The Journal Of Immunology 2020, 204: 1661-1673. PMID: 32060136, PMCID: PMC7755271, DOI: 10.4049/jimmunol.1900922.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAgingAntibodies, ViralCohort StudiesFemaleGene Expression ProfilingHemagglutination Inhibition TestsHumansImmunogenicity, VaccineInfluenza A virusInfluenza VaccinesInfluenza, HumanMaleNK Cell Lectin-Like Receptor Subfamily BOligonucleotide Array Sequence AnalysisSeasonsTranscriptomeVaccinationVaccines, InactivatedYoung AdultConceptsVaccine-induced Ab responsesOlder adultsInfluenza vaccinationDays postvaccinationInfluenza vaccineAb responsesMore effective influenza vaccinesImportant public health toolInactivated influenza vaccinationSeasonal influenza vaccineVaccine-induced immunityEffective influenza vaccinesMolecular signaturesEffects of immunosenescencePublic health toolImmune signaturesVaccination seasonVaccine responsesVaccine compositionSubset of individualsAge groupsHealth toolsSingle age groupAdultsPostvaccination
2016
Age‐associated vascular inflammation promotes monocytosis during atherogenesis
Du W, Wong C, Song Y, Shen H, Mori D, Rotllan N, Price N, Dobrian AD, Meng H, Kleinstein SH, Fernandez‐Hernando C, Goldstein DR. Age‐associated vascular inflammation promotes monocytosis during atherogenesis. Aging Cell 2016, 15: 766-777. PMID: 27135421, PMCID: PMC4933655, DOI: 10.1111/acel.12488.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAortaAtherosclerosisBlood VesselsCell CountChemotaxisCulture Media, ConditionedDiet, High-FatDown-RegulationHematopoiesisHemodynamicsInflammationInflammation MediatorsInsulin ResistanceInterleukin-6LeukocytosisMacrophagesMaleMiceMice, Inbred C57BLMonocytesOligonucleotide Array Sequence AnalysisReceptors, LDLStromal CellsUp-RegulationConceptsHigh-fat dietVascular inflammationMacrophage accumulationAtherosclerotic aortaBone marrow transplant experimentsStromal factorsElevated blood pressureVascular smooth muscle cellsLow-fat dietSmooth muscle cellsBlood pressurePeripheral monocytosisProinflammatory stateInflammatory stateLDL levelsIL-6Insulin resistancePeripheral bloodEnhanced atherogenesisInflammatory responseMetabolic dysfunctionYoung aortasMurine modelProduction of osteopontinCCL-2
2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, Kleinstein SH, Kaech SM. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. Journal Of Experimental Medicine 2015, 212: 2041-2056. PMID: 26503446, PMCID: PMC4647261, DOI: 10.1084/jem.20150186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCluster AnalysisFlow CytometryHomeodomain ProteinsHost-Pathogen InteractionsLectins, C-TypeLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutMice, TransgenicOligonucleotide Array Sequence AnalysisProtein BindingReceptors, ImmunologicRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionT-Box Domain ProteinsT-Lymphocytes, CytotoxicTranscriptomeZinc Finger E-box Binding Homeobox 2ConceptsTerminal differentiationT cell terminal differentiationChromatin immunoprecipitation sequencingNovel genetic pathwaysTranscription factor ZEB2Cell terminal differentiationZeb2 functionImmunoprecipitation sequencingMemory cell potentialDifferentiation programGenetic pathwaysCytotoxic T lymphocyte differentiationTerminal effectorZEB2 mRNAPrecursor cellsCoordinated actionLymphocyte differentiationT lymphocyte differentiationMemory precursor cellsGenesT-betDifferentiationViral infectionZEB2CooperateAging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, Belshe RB, Kaech SM, Shadel GS, Kleinstein SH, Shaw AC. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging 2015, 7: 38-51. PMID: 25596819, PMCID: PMC4356402, DOI: 10.18632/aging.100720.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAgingCells, CulturedDNA, MitochondrialFemaleGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansInfluenza VaccinesInfluenza, HumanLeukocytes, MononuclearMaleMitochondriaMitochondrial TurnoverOligonucleotide Array Sequence AnalysisOxidative PhosphorylationSeasonsTime FactorsTreatment OutcomeVaccinationYoung AdultConceptsPlasma cell signatureDay 2Influenza vaccinationDay 7Cell signatureOlder adultsInfluenza vaccine responsesAdults meeting criteriaType I interferon responseAge-associated impairmentAge-dependent alterationsI interferon responseMitochondrial biogenesisResponse signatureVaccine seasonVaccine respondersFrail subjectsInfluenza vaccineVaccine responsesVaccine responsivenessGene expression microarray analysisAbsent responseYounger respondersDay 28Meeting criteria
2014
TLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation
Cui W, Joshi NS, Liu Y, Meng H, Kleinstein SH, Kaech SM. TLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation. The Journal Of Immunology 2014, 192: 4221-4232. PMID: 24659688, PMCID: PMC4071140, DOI: 10.4049/jimmunol.1302569.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsCD8-Positive T-LymphocytesCell DifferentiationImmunologic MemoryLigandsLipid ALipopolysaccharidesLymphocyte ActivationMiceMice, TransgenicOligonucleotide Array Sequence AnalysisToll-Like Receptor 4VaccinationConceptsT cell differentiationT cellsEffector cellsTLR ligandsToll/IL-1R domain-containing adapterClonal expansionMore memory T cellsMemory T cellsT cell memoryEffector cell expansionTLR4 ligand LPSMonophosphoryl lipid ARole of adjuvantsTLR4 ligand lipopolysaccharideCell differentiationGene expression signaturesMemory CD8LPS-TLR4TLR4 ligandMonophosphoryl lipidLigand LPSLigand lipopolysaccharideAb productionSecondary infectionCell memory
2012
The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response
Bolen CR, Robek MD, Brodsky L, Schulz V, Lim JK, Taylor MW, Kleinstein SH. The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response. Journal Of Interferon & Cytokine Research 2012, 33: 15-23. PMID: 23067362, PMCID: PMC3539252, DOI: 10.1089/jir.2012.0037.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHCV patientsHealthy volunteersChronic hepatitis C virus (HCV) infectionChronic hepatitis C virusInfected individualsTreatment-naïve HCV patientsHepatitis C virus infectionBlood transcriptional profilesBlood transcriptional signaturesC virus infectionChronic HCV infectionOngoing immune responseBlood mononuclear cellsHepatitis C virusBlood transcriptional profilingDrug treatment responseHCV infectionSubset of IFNMononuclear cellsC virusIFN signatureHealthy controlsTreatment responseVirus infection
2011
Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis
Protiva P, Mason JB, Liu Z, Hopkins ME, Nelson C, Marshall JR, Lambrecht RW, Pendyala S, Kopelovich L, Kim M, Kleinstein SH, Laird PW, Lipkin M, Holt PR. Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis. Cancer Prevention Research 2011, 4: 530-543. PMID: 21321062, PMCID: PMC3742550, DOI: 10.1158/1940-6207.capr-10-0143.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiological AvailabilityCell Transformation, NeoplasticColonColorectal NeoplasmsDietary SupplementsDNA BreaksDNA MethylationFemaleFolic AcidFolic Acid DeficiencyGene ExpressionGene Expression ProfilingHumansMaleMiddle AgedOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticRectumReverse Transcriptase Polymerase Chain ReactionTumor Suppressor Protein p53ConceptsFolate supplementationFolate deliveryFolate depletionImmune responseColorectal carcinogenesisDNA strand breaksHuman colonColorectal cancer riskFolic acidSupplemental folic acidLow-folate dietLow folate statusImmune response pathwaysImmune-related pathwaysFirst studyRectosigmoid biopsiesRisk volunteersPrimary endpointGene array analysisPromoter-specific DNA methylationRepletion protocolFolate dietFolate levelsSecond studyFolate status
2010
Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation
Frucht CS, Uduman M, Duke JL, Kleinstein SH, Santos-Sacchi J, Navaratnam DS. Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation. PLOS ONE 2010, 5: e11502. PMID: 20634979, PMCID: PMC2901389, DOI: 10.1371/journal.pone.0011502.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationChickensColforsinEnzyme ActivatorsGene Expression RegulationHair Cells, AuditoryMicroRNAsOligonucleotide Array Sequence AnalysisOrgan Culture TechniquesOrgan of CortiPolymerase Chain ReactionConceptsNew hair cellsAuditory epitheliumChicken auditory epitheliumHair cellsInner ear developmentHair cell regenerationGene expression analysisAuditory hair cellsEar developmentExpression analysisMyosin VIEnrichment analysisCycle controlGene expressionMolecular eventsSingle microRNAMediator of proliferationRelevant pathwaysFunctional experimentsPost-hatch chicksRegenerating tissueMammalsGenesBrdU incorporationCell regenerationLambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities
Pagliaccetti NE, Chu EN, Bolen CR, Kleinstein SH, Robek MD. Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities. Virology 2010, 401: 197-206. PMID: 20303135, PMCID: PMC2864496, DOI: 10.1016/j.virol.2010.02.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedCytokinesGene Expression ProfilingHepatitis B virusHepatocytesHumansInterferon-alphaInterleukinsMiceMice, TransgenicOligonucleotide Array Sequence AnalysisVirus ReplicationConceptsIFN-alpha/betaIFN-lambdaHepatitis B virus replicationB virus replicationType III interferonsRelated cytokines interleukinWeak antiviral activityHBV responseHBV replicationIL-22IL-6Molecular mechanismsCytokines interleukinAlpha interferonAntiviral immunityIII interferonsTransgenic miceAntiviral responseAntiviral mechanismAntiviral activityVirus replicationUnique receptorCommon molecular mechanismIFN-lambda2Vivo activityAntiviral Response Dictated by Choreographed Cascade of Transcription Factors
Zaslavsky E, Hershberg U, Seto J, Pham AM, Marquez S, Duke JL, Wetmur JG, tenOever BR, Sealfon SC, Kleinstein SH. Antiviral Response Dictated by Choreographed Cascade of Transcription Factors. The Journal Of Immunology 2010, 184: 2908-2917. PMID: 20164420, PMCID: PMC2856074, DOI: 10.4049/jimmunol.0903453.Peer-Reviewed Original ResearchMeSH KeywordsConserved SequenceDendritic CellsGene Expression Regulation, ViralGenes, OverlappingHumansMonocytesMultigene FamilyNewcastle disease virusOligonucleotide Array Sequence AnalysisPredictive Value of TestsPromoter Regions, GeneticReproducibility of ResultsTranscription FactorsUp-RegulationConceptsCell state transitionsRegulatory networksTranscription factorsGenetic programMost individual genesNovel transcription factorSpecific transcription factorsSingle regulatory networkAntiviral responseGene expression changesCurrent biological knowledgeActivation of RIGChoreographed cascadePromoter analysisIndividual genesGenetic regulatory networksMaster regulatorExpression changesBiological knowledgeExpression kineticsImmune evasion genesAntiviral roleImmune antagonistsHost immune systemNewcastle disease virus
2009
Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells
Bruno VM, Hannemann S, Lara-Tejero M, Flavell RA, Kleinstein SH, Galán JE. Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells. PLOS Pathogens 2009, 5: e1000538. PMID: 19662166, PMCID: PMC2714975, DOI: 10.1371/journal.ppat.1000538.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBlotting, WesternCell LineColitisEpithelial CellsGene ExpressionGene Expression ProfilingGuanine Nucleotide Exchange FactorsHumansImmunity, InnateMiceMitogen-Activated Protein Kinase KinasesMyotonin-Protein KinaseNF-kappa BOligonucleotide Array Sequence AnalysisProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionSalmonella InfectionsSalmonella typhimuriumSignal TransductionTranscription, GeneticConceptsInnate immune receptorsInnate immune responseIntestinal inflammationImmune responseEpithelial cellsBacterial productsIntestinal inflammatory pathologyImmune receptorsCultured epithelial cellsEnteric pathogen Salmonella typhimuriumInnate immune systemIntestinal epithelial cellsInflammatory pathologyInflammatory responseType III secretion effectorsImmune systemSalmonella typhimuriumNF-kappaBMitogen-activated protein kinaseEnteric pathogensPathogen Salmonella typhimuriumPathologyReceptorsInflammationType III secretion system