Featured Publications
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.Peer-Reviewed Original ResearchConceptsMild COVID-19Control individualsInnate immune genesInfluenza vaccinationCOVID-19Day 28Day 1Viral infectionNon-hospitalized COVID-19Baseline immune statusAcute viral infectionSex-matched control individualsMemory-like CD8IL-15 responsesIL-15 stimulationSex-dimorphic effectsToll-like receptorsFuture immune responseHealthy control individualsImmune genesSystems immunology approachT-cell activation signaturesHealthy male individualsMale individualsMore IFNγBroad 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 responseCancer prognosis with shallow tumor RNA sequencing
Milanez-Almeida P, Martins A, Germain R, Tsang J. Cancer prognosis with shallow tumor RNA sequencing. Nature Medicine 2020, 26: 188-192. PMID: 32042193, DOI: 10.1038/s41591-019-0729-3.Peer-Reviewed Original ResearchConceptsCancer prognosisTumor RNA-seq dataTumor RNA sequencingPrediction of outcomeTypes of cancerClinical outcomesRNA sequencingAdverse outcomesRelative riskDisease outcomeOutcome predictionTumor RNA-seqPersonalized oncologyTranscriptional signatureCancer1–3Molecular pathwaysOutcomesPrognosisLongitudinal analysisTranscriptional pathwaysCancerSystematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations
Lu Y, Biancotto A, Cheung F, Remmers E, Shah N, McCoy J, Tsang J. Systematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations. Immunity 2016, 45: 1162-1175. PMID: 27851916, PMCID: PMC6532399, DOI: 10.1016/j.immuni.2016.10.025.Peer-Reviewed Original ResearchConceptsExpression variationDisease-associated genetic polymorphismsSingle-cell dataPrimary cell populationsCell populationsOrganismal levelFunctional associationDisease susceptibilityGenetic associationFlow cytometry dataCytometry dataGenetic polymorphismsHuman cohortsFlow cytometryCellsHigh-dimensional flow cytometryCell subpopulationsImportant rolePrevalent featureProteinPhenotypeSystematic analysisMultiple baseline measurementsPolymorphismPopulationA crowdsourcing approach for reusing and meta-analyzing gene expression data
Shah N, Guo Y, Wendelsdorf K, Lu Y, Sparks R, Tsang J. A crowdsourcing approach for reusing and meta-analyzing gene expression data. Nature Biotechnology 2016, 34: 803-806. PMID: 27323300, PMCID: PMC6871002, DOI: 10.1038/nbt.3603.Peer-Reviewed Original ResearchUtilizing population variation, vaccination, and systems biology to study human immunology
Tsang J. Utilizing population variation, vaccination, and systems biology to study human immunology. Trends In Immunology 2015, 36: 479-493. PMID: 26187853, PMCID: PMC4979540, DOI: 10.1016/j.it.2015.06.005.Peer-Reviewed Original ResearchGlobal 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 variationVaccinationTitersIntegrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint
Mulè M, Martins A, Cheung F, Farmer R, Sellers B, Quiel J, Jain A, Kotliarov Y, Bansal N, Chen J, Schwartzberg P, Tsang J. Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint. Immunity 2024, 57: 1160-1176.e7. PMID: 38697118, DOI: 10.1016/j.immuni.2024.04.009.Peer-Reviewed Original ResearchConceptsTranscriptional statesVaccine responseSingle-cell profiling methodsSingle-cell variationAS03-adjuvanted vaccineUnadjuvanted influenza vaccineResponse to lipopolysaccharide stimulationB cell signaturesCD14<sup>+</sup> monocytesSingle-cell levelBiological insightsUnadjuvanted vaccineAS03-adjuvantedInfluenza vaccineResponse phenotypesCITE-seqInnate subsetsAdjuvant developmentHigh antibody respondersDay 1Antibody respondersLipopolysaccharide stimulationVaccineCorrelation networkHuman populationImproving Vaccine-Induced Immunity: Can Baseline Predict Outcome?
Tsang J, Dobaño C, VanDamme P, Moncunill G, Marchant A, Othman R, Sadarangani M, Koff W, Kollmann T. Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome? Trends In Immunology 2020, 41: 457-465. PMID: 32340868, PMCID: PMC7142696, DOI: 10.1016/j.it.2020.04.001.Peer-Reviewed Original Research
2023
Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine
Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han K, Rachmaninoff N, Pietz H, Wang K, Tsang J, Cohen J. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. ELife 2023, 12: e80652. PMID: 36648132, PMCID: PMC9844983, DOI: 10.7554/elife.80652.Peer-Reviewed Original ResearchConceptsEarly innate responseVaccine recipientsPrior exposureInnate responseType I interferon signatureInfectious diseasesSeronegative vaccine recipientsType I IFN responseEarly antiviral responseNational InstituteInnate immune responseSystems immunology approachI IFN responseAdaptive immune phenotypesIntramural Research ProgramInterferon signatureAntibody titersVaccine trialsImmune phenotypeVirus vaccineNaive womenImmune responseSanofi PasteurDay 1Herpesvirus vaccine
2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, PMCID: PMC10777159, DOI: 10.1038/s41590-022-01367-z.Peer-Reviewed Original ResearchConceptsT cell receptorImmune responseGerminal centersPrevious SARS-CoV-2 infectionSARS-CoV-2 infectionB-cell receptor sequencingTissue-specific immunityCell receptor sequencingAdaptive immune responsesUpper respiratory tractMemory B cellsT cell clonotypesSite of infectionSARS-CoV-2Pharyngeal lymphoid tissuePeripheral bloodLymphocyte populationsLymphoid tissueRespiratory tractCell clonotypesAdaptive immunityB cellsCDR3 sequencesAdenoidsCell receptorConsidering innate immune responses in SARS-CoV-2 infection and COVID-19
Diamond M, Lambris J, Ting J, Tsang J. Considering innate immune responses in SARS-CoV-2 infection and COVID-19. Nature Reviews Immunology 2022, 22: 465-470. PMID: 35788185, PMCID: PMC9252555, DOI: 10.1038/s41577-022-00744-x.Peer-Reviewed Original ResearchImmunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Sacco K, Castagnoli R, Vakkilainen S, Liu C, Delmonte OM, Oguz C, Kaplan IM, Alehashemi S, Burbelo PD, Bhuyan F, de Jesus AA, Dobbs K, Rosen LB, Cheng A, Shaw E, Vakkilainen MS, Pala F, Lack J, Zhang Y, Fink DL, Oikonomou V, Snow AL, Dalgard CL, Chen J, Sellers BA, Montealegre Sanchez GA, Barron K, Rey-Jurado E, Vial C, Poli MC, Licari A, Montagna D, Marseglia GL, Licciardi F, Ramenghi U, Discepolo V, Lo Vecchio A, Guarino A, Eisenstein EM, Imberti L, Sottini A, Biondi A, Mató S, Gerstbacher D, Truong M, Stack MA, Magliocco M, Bosticardo M, Kawai T, Danielson JJ, Hulett T, Askenazi M, Hu S, Cohen J, Su H, Kuhns D, Lionakis M, Snyder T, Holland S, Goldbach-Mansky R, Tsang J, Notarangelo L. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nature Medicine 2022, 28: 1050-1062. PMID: 35177862, PMCID: PMC9119950, DOI: 10.1038/s41591-022-01724-3.Peer-Reviewed Original ResearchConceptsInflammatory syndromeSevere acute respiratory syndrome coronavirus 2Pediatric coronavirus disease 2019Acute respiratory syndrome coronavirus 2Robust type I interferon (IFN) responseRespiratory syndrome coronavirus 2Pediatric COVID-19Pediatric healthy controlsSignatures of inflammationMultisystem inflammatory syndromeTime of admissionSyndrome coronavirus 2Combination of HLAT cell clonotypesType I interferon responseCoronavirus disease 2019Multi-institutional studyCOVID-19Minority of childrenT cell activationI interferon responseType II IFNSubstantial morbidityCoronavirus 2PCR status
2021
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease
Ozen A, Kasap N, Vujkovic-Cvijin I, Apps R, Cheung F, Karakoc-Aydiner E, Akkelle B, Sari S, Tutar E, Ozcay F, Uygun DK, Islek A, Akgun G, Selcuk M, Sezer OB, Zhang Y, Kutluk G, Topal E, Sayar E, Celikel C, Houwen RHJ, Bingol A, Ogulur I, Eltan SB, Snow AL, Lake C, Fantoni G, Alba C, Sellers B, Chauvin SD, Dalgard CL, Harari O, Ni YG, Wang MD, Devalaraja-Narashimha K, Subramanian P, Ergelen R, Artan R, Guner SN, Dalgic B, Tsang J, Belkaid Y, Ertem D, Baris S, Lenardo MJ. Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease. Nature Immunology 2021, 22: 128-139. PMID: 33398182, PMCID: PMC7856263, DOI: 10.1038/s41590-020-00830-z.Peer-Reviewed Original ResearchConceptsBlockade of C5Complement C5 inhibitorInnate immune complement systemOveractivation of complementComplement regulatory proteins CD55Healthy gut microbiomeImmune complement systemCD55 deficiencyComplement hyperactivationImmune recoveryImmunoglobulin replacementGastrointestinal pathologyNormal immunityC5 inhibitionC5 inhibitorImmunoglobulin concentrationsMedical treatmentPathophysiological manifestationsInnate immunityLethal diseaseGut microbiomeProteins CD55Complement systemDiseaseHuman data
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
2017
Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network
Martins A, Narayanan M, Prüstel T, Fixsen B, Park K, Gottschalk R, Lu Y, Andrews-Pfannkoch C, Lau W, Wendelsdorf K, Tsang J. Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network. Cell Systems 2017, 4: 379-392.e12. PMID: 28365150, PMCID: PMC8392141, DOI: 10.1016/j.cels.2017.03.002.Peer-Reviewed Original ResearchConceptsGene networksCellular adaptationCell variationSingle-cell transcriptomic studiesGene-gene correlationsUnderlying regulatory mechanismsDegree of phosphorylationPhenotypic diversityTranscriptomic studiesEnvironmental adaptationMultiple molecular parametersGene expressionRegulatory mechanismsCellular heterogeneityDistinct environmentsSingle cellsHuman macrophagesQuantitative tuningCell populationsNatural perturbationsGenesDifferent environmentsSuch variationCellsStochastic simulation analysis
2016
Solving Immunology?
Vodovotz Y, Xia A, Read EL, Bassaganya-Riera J, Hafler DA, Sontag E, Wang J, Tsang JS, Day JD, Kleinstein SH, Butte AJ, Altman MC, Hammond R, Sealfon SC. Solving Immunology? Trends In Immunology 2016, 38: 116-127. PMID: 27986392, PMCID: PMC5695553, DOI: 10.1016/j.it.2016.11.006.Peer-Reviewed Original Research
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