Featured Publications
Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus
Kotliarov Y, Sparks R, Martins A, Mulè M, Lu Y, Goswami M, Kardava L, Banchereau R, Pascual V, Biancotto A, Chen J, Schwartzberg P, Bansal N, Liu C, Cheung F, Moir S, Tsang J. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nature Medicine 2020, 26: 618-629. PMID: 32094927, PMCID: PMC8392163, DOI: 10.1038/s41591-020-0769-8.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdolescentAdultAgedAged, 80 and overAntibody FormationB-LymphocytesChildChild, PreschoolCohort StudiesFemaleGene Expression ProfilingHumansInfluenza VaccinesInfluenza, HumanLupus Erythematosus, SystemicMaleMiddle AgedTranscriptomeVaccinationYellow FeverYellow Fever VaccineYoung AdultConceptsDisease activityVaccine responsivenessAutoimmune disease activityBlood transcriptional signaturesYellow fever vaccinationSystemic lupus erythematosusClinical quiescenceFever vaccinationLupus erythematosusCancer immunotherapyBaseline predictorsDisease outcomeHealthy subjectsImmune responseI IFNHealthy individualsVaccinationTranscriptional signatureImmune variationBaseline statePatientsExtent of activationBiological basisSurface proteinsInfection responseGlobal Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses
Tsang J, Schwartzberg P, Kotliarov Y, Biancotto A, Xie Z, Germain R, Wang E, Olnes M, Narayanan M, Golding H, Moir S, Dickler H, Perl S, Cheung F, Center T, Consortium T, Obermoser G, Chaussabel D, Palucka K, Chen J, Fuchs J, Ho J, Khurana S, King L, Langweiler M, Liu H, Manischewitz J, Pos Z, Posada J, Schum P, Shi R, Valdez J, Wang W, Zhou H, Kastner D, Marincola F, McCoy J, Trinchieri G, Young N. Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses. Cell 2014, 157: 499-513. PMID: 24725414, PMCID: PMC4139290, DOI: 10.1016/j.cell.2014.03.031.Peer-Reviewed Original ResearchConceptsPre-existing antibody titersPostvaccination antibody responsePeripheral blood mononuclear cell transcriptomeB cell responsesBaseline time pointPostvaccination responsesInfluenza vaccinationImmune monitoringSerum titersAntibody titersAntibody responseBaseline predictorsBaseline differencesImmune parametersHuman immunityCell responsesSubpopulation frequenciesTime pointsCell populationsIntra-individual variationVaccinationTiters
2023
Inflammatory and interferon gene expression signatures in patients with mitochondrial disease
Warren E, Gordon-Lipkin E, Cheung F, Chen J, Mukherjee A, Apps R, Tsang J, Jetmore J, Schlein M, Kruk S, Lei Y, West A, McGuire P. Inflammatory and interferon gene expression signatures in patients with mitochondrial disease. Journal Of Translational Medicine 2023, 21: 331. PMID: 37208779, PMCID: PMC10199642, DOI: 10.1186/s12967-023-04180-w.Peer-Reviewed Original ResearchConceptsMTD patientsHealthy controlsMitochondrial dysfunctionAntiviral responseInterferon gene expression signatureChronic inflammatory disordersType I interferonCommon gene signaturePeripheral inflammationGene expression signaturesImmune dysregulationChronic inflammationMetabolic decompensationInflammatory disordersInterleukin-1βSymptom progressionT cellsInflammatory signalingMouse modelI interferonMitochondrial diseasePatientsTranslational evidenceMELAS patientsDysfunction
2021
Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19
Liu C, Martins AJ, Lau WW, Rachmaninoff N, Chen J, Imberti L, Mostaghimi D, Fink DL, Burbelo PD, Dobbs K, Delmonte OM, Bansal N, Failla L, Sottini A, Quiros-Roldan E, Lee Han K, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS, , Rossi C, Su H, Kuhns D, Cohen J, Notarangelo L, Tsang J, , Abers M, Apps R, Bosticardo M, Milanez-Almeida P, Mulè M, Shaw E, Zhang Y, , Castelli F, Muiesan M, Tomasoni G, Scolari F, Tucci A. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell 2021, 184: 1836-1857.e22. PMID: 33713619, PMCID: PMC7874909, DOI: 10.1016/j.cell.2021.02.018.Peer-Reviewed Original ResearchConceptsFatal COVID-19Peripheral immune cellsPlasmacytoid dendritic cellsPost-symptom onsetCOVID-19 patientsCOVID-19Fatty acid metabolismGene expression signaturesNK cellsSymptom onsetDendritic cellsSevere patientsFatal outcomeImmune response variationCellular inflammationImmune cellsInflammatory responseCell receptor sequencesExtensive patientClinical monitoringTherapeutic interventionsCell activationDay 17Disease severitySigns of exhaustion
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19
2016
Effects of Systemically Administered Hydrocortisone on the Human Immunome
Olnes M, Kotliarov Y, Biancotto A, Cheung F, Chen J, Shi R, Zhou H, Wang E, Tsang J, Nussenblatt R. Effects of Systemically Administered Hydrocortisone on the Human Immunome. Scientific Reports 2016, 6: 23002. PMID: 26972611, PMCID: PMC4789739, DOI: 10.1038/srep23002.Peer-Reviewed Original ResearchMeSH KeywordsAdultB-Lymphocyte SubsetsCluster AnalysisDose-Response Relationship, DrugFemaleFlow CytometryGene Expression ProfilingHumansHydrocortisoneImmunophenotypingInfusions, IntravenousKiller Cells, NaturalLymphocyte CountLymphocyte SubsetsMaleMiddle AgedSignal TransductionTime FactorsT-Lymphocyte SubsetsTranscriptomeYoung AdultConceptsSystemic corticosteroid administrationNK cell numbersHigh-dimensional flow cytometryEffect of corticosteroidsNatural killer cellsT cell subsetsEffects of systemicallyImmune system parametersAdministration of hydrocortisoneNF-κB signalingPaucity of dataHuman immunomeIntravenous hydrocortisoneCorticosteroid administrationLymphocyte subsetsNK cellsKiller cellsCell subsetsHC infusionsT cellsT lymphocytesHealthy humansGlucocorticoid receptorLow dosesCorticosteroids
2014
Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals
Kardava L, Moir S, Shah N, Wang W, Wilson R, Buckner CM, Santich BH, Kim LJ, Spurlin EE, Nelson AK, Wheatley AK, Harvey CJ, McDermott AB, Wucherpfennig KW, Chun TW, Tsang JS, Li Y, Fauci AS. Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals. Journal Of Clinical Investigation 2014, 124: 3252-3262. PMID: 24892810, PMCID: PMC4071400, DOI: 10.1172/jci74351.Peer-Reviewed Original ResearchConceptsHIV-specific responsesMemory B cellsB cellsInfected individualsMemory subsetsUninfected individualsVirus-specific B cell responsesMemory B cell subsetsPeripheral blood B cellsCertain infected individualsHIV-specific antibodiesB cell abnormalitiesAbnormal B cellsB-cell dysfunctionB cell responsesBlood B cellsB cell subsetsStage of infectionPlasma viremiaAntiretroviral therapyHIV antibodiesHIV diseaseHIV infectionImmune activationCell subsets
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