2015
The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales
Yaari G, Benichou JI, Vander Heiden J, Kleinstein SH, Louzoun Y. The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales. Philosophical Transactions Of The Royal Society B Biological Sciences 2015, 370: 20140242. PMID: 26194756, PMCID: PMC4528419, DOI: 10.1098/rstb.2014.0242.Peer-Reviewed Original ResearchMeSH KeywordsAntibody AffinityAntibody DiversityB-LymphocytesCell LineageClonal Selection, Antigen-MediatedComplementarity Determining RegionsGenes, ImmunoglobulinHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionModels, GeneticModels, ImmunologicalMutationReceptors, Antigen, B-CellSomatic Hypermutation, ImmunoglobulinTime FactorsConceptsLineage treesPositive selectionStrong selection pressureLong-term selectionInfluence of selectionGene familyVariable gene familiesComplementarity determining regionsClone membersMutation patternsSelection pressureB cell populationsImmunoglobulin genesB cellsFramework regionsSomatic hypermutationSomatic mutationsAffinity maturationMutationsClone sizeMaturation processLong trunkAffinity maturation processSignificant diversityMultiple roundsComparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism
Thakar J, Hartmann BM, Marjanovic N, Sealfon SC, Kleinstein SH. Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism. BMC Immunology 2015, 16: 46. PMID: 26272204, PMCID: PMC4536893, DOI: 10.1186/s12865-015-0107-y.Peer-Reviewed Original ResearchConceptsTranscription factor activityImmune antagonismExpression profilesGenome-wide expression profilesGenome-wide transcriptional profiling dataFactor activityGenome-wide transcriptional profilesTranscription factor SATB1DNA-binding sitesTranscriptional profiling dataHost-pathogen interactionsGene expression profilesISGF3 activityTranscriptional responseTranscription factorsTranscriptional profilesHost interactionsProfiling dataApplication of betaNovel effectMechanistic insightsInfected cellsInfluenza A virusesMechanistic differencesNewcastle disease virusHuman Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses
Hartmann BM, Thakar J, Albrecht RA, Avey S, Zaslavsky E, Marjanovic N, Chikina M, Fribourg M, Hayot F, Schmolke M, Meng H, Wetmur J, García-Sastre A, Kleinstein SH, Sealfon SC. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses. Journal Of Virology 2015, 89: 10190-10205. PMID: 26223639, PMCID: PMC4580178, DOI: 10.1128/jvi.01523-15.Peer-Reviewed Original ResearchMeSH KeywordsAntigenic VariationDendritic CellsEuropeGene Expression ProfilingGene Expression RegulationHistory, 20th CenturyHistory, 21st CenturyHost-Pathogen InteractionsHumansInfluenza A Virus, H1N1 SubtypeInfluenza Pandemic, 1918-1919Influenza, HumanInterferonsMolecular EpidemiologyNF-kappa BPandemicsReassortant VirusesRecombination, GeneticSeasonsSignal TransductionTime FactorsUnited StatesConceptsHuman dendritic cellsDendritic cellsImmune responseInfluenza virusSeasonal strainsNF-κBSeasonal H1N1 influenza virusHuman influenza virus infectionH1N1 influenza strainInterferon-stimulated gene responseSeasonal influenza virusesInfluenza virus infectionH1N1 influenza virusStrain-dependent differencesClinical severityVirus infectionInfluenza strainsAntiviral programViral infectionPandemic strainsHost responseAntigenic driftInfectionH postinfectionSelective inductionAging-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
High-resolution antibody dynamics of vaccine-induced immune responses
Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden J, Kelton W, Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM. High-resolution antibody dynamics of vaccine-induced immune responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4928-4933. PMID: 24639495, PMCID: PMC3977259, DOI: 10.1073/pnas.1323862111.Peer-Reviewed Original ResearchDynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression
Bolen CR, Ding S, Robek MD, Kleinstein SH. Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology 2014, 59: 1262-1272. PMID: 23929627, PMCID: PMC3938553, DOI: 10.1002/hep.26657.Peer-Reviewed Original ResearchConceptsGene expressionExpression profilingIndividual interferonMicroarray-based gene expression profilingDynamic expression profilingGene expression profilingSimilar signaling cascadesPotential specific rolesPromoter analysisTranscriptional responseHuh7 hepatoma cellsGene inductionExpression hierarchySignaling cascadesIFN-α signalingAntiviral stateNegative feedback mechanismType IPrimary human hepatocytesHepatoma cellsISG inductionSpecific roleGenesInterferon-stimulated gene inductionSuperior clinical activity
2007
Definition of Germinal-Center B Cell Migration In Vivo Reveals Predominant Intrazonal Circulation Patterns
Hauser AE, Junt T, Mempel TR, Sneddon MW, Kleinstein SH, Henrickson SE, von Andrian UH, Shlomchik MJ, Haberman AM. Definition of Germinal-Center B Cell Migration In Vivo Reveals Predominant Intrazonal Circulation Patterns. Immunity 2007, 26: 655-667. PMID: 17509908, DOI: 10.1016/j.immuni.2007.04.008.Peer-Reviewed Original Research