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 IFNγNormalizing and denoising protein expression data from droplet-based single cell profiling
Mulè M, Martins A, Tsang J. Normalizing and denoising protein expression data from droplet-based single cell profiling. Nature Communications 2022, 13: 2099. PMID: 35440536, PMCID: PMC9018908, DOI: 10.1038/s41467-022-29356-8.Peer-Reviewed Original ResearchConceptsProtein expression dataSingle-cell profiling methodsExpression dataSingle-cell profilingOligo-conjugated antibodiesTechnical noiseProtein populationCITE-seqCellular heterogeneityComprehensive dissectionDownstream analysisCell profilingDSBsSingle cellsProtein levelsProtein expressionCell populationsOpen-source R packageProfiling methodProtein countsEmpty dropletsR packageComputational analysisCellsBiological variationA local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells
Wong H, Park K, Gola A, Baptista A, Miller C, Deep D, Lou M, Boyd L, Rudensky A, Savage P, Altan-Bonnet G, Tsang J, Germain R. A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells. Cell 2021, 184: 3981-3997.e22. PMID: 34157301, PMCID: PMC8390950, DOI: 10.1016/j.cell.2021.05.028.Peer-Reviewed Original ResearchTime-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, Han KL, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS; NIAID COVID Consortium; COVID Clinicians; Rossi C, Su HC, Kuhns DB, Cohen JI, Notarangelo LD, Tsang JS. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell. 2021 Apr 1;184(7):1836-1857.e22. doi: 10.1016/j.cell.2021.02.018. Epub 2021 Feb 10. PMID: 33713619; PMCID: PMC7874909.Peer-Reviewed Original ResearchBroad 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 populationA unified metric of human immune health
Sparks R, Rachmaninoff N, Lau W, Hirsch D, Bansal N, Martins A, Chen J, Liu C, Cheung F, Failla L, Biancotto A, Fantoni G, Sellers B, Chawla D, Howe K, Mostaghimi D, Farmer R, Kotliarov Y, Calvo K, Palmer C, Daub J, Foruraghi L, Kreuzburg S, Treat J, Urban A, Jones A, Romeo T, Deuitch N, Moura N, Weinstein B, Moir S, Ferrucci L, Barron K, Aksentijevich I, Kleinstein S, Townsley D, Young N, Frischmeyer-Guerrerio P, Uzel G, Pinto-Patarroyo G, Cudrici C, Hoffmann P, Stone D, Ombrello A, Freeman A, Zerbe C, Kastner D, Holland S, Tsang J. A unified metric of human immune health. Nature Medicine 2024, 30: 2461-2472. PMID: 38961223, DOI: 10.1038/s41591-024-03092-6.Peer-Reviewed Original ResearchClinically healthy individualsHealthy individualsImmune cell frequenciesImmune healthInflammatory biomarkers C-reactive proteinC-reactive proteinBiomarkers C-reactive proteinResponse to immunizationAntibody response to immunizationInflammatory disease statesImmune pathologyDisease activityTreatment responseAntigenic stimulationImmune consequencesClinical dataImmunological pathwaysHealthy controlsCell frequencyInterleukin-6Nonimmunologic diseasesImmune diseasesMonogenic diseasesMonogenic conditionsMedication useImproving 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
2024
Acute and persistent responses after H5N1 vaccination in humans
Apps R, Biancotto A, Candia J, Kotliarov Y, Perl S, Cheung F, Farmer R, Mulè M, Rachmaninoff N, Chen J, Martins A, Shi R, Zhou H, Bansal N, Schum P, Olnes M, Milanez-Almeida P, Han K, Sellers B, Cortese M, Hagan T, Rouphael N, Pulendran B, King L, Manischewitz J, Khurana S, Golding H, van der Most R, Dickler H, Germain R, Schwartzberg P, Tsang J. Acute and persistent responses after H5N1 vaccination in humans. Cell Reports 2024, 43: 114706. PMID: 39235945, DOI: 10.1016/j.celrep.2024.114706.Peer-Reviewed Original ResearchH5N1 influenza vaccineImpact vaccine responsesTime pointsAdjuvant AS03H5N1 vaccineInfluenza vaccineT cellsVaccine responseVaccinated cohortHigh antibody respondersImmune stateVaccine antigensMultiple time pointsSingle-cell profilingInitial vaccinationSystems immunologyVaccinePersistent responseSurface proteinsCell type-specific signaturesChromatin accessibilityTranscription factorsH5N1DaysAS03Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley P, Long S, Liu C, Koroleva G, Martins A, Tsang J, Herold K. Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes. Journal Of Clinical Investigation 2024, 134: e177492. PMID: 39137044, PMCID: PMC11405034, DOI: 10.1172/jci177492.Peer-Reviewed Original ResearchCD8+ T cellsAutoreactive T cellsT cellsType 1 diabetesPeripheral blood CD8+ T cellsBlood CD8+ T cellsExpansion of autoreactive T cellsOperational toleranceExpression of CD127Progression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireT cell receptorAt-risk patientsAnalysis of study participantsStudy participantsIL7R expressionTeplizumab groupCD8+Placebo groupCD4+Clinical respondersFree intervalTeplizumabReduced expression of genesLicensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus
Khurana S, King L, Manischewitz J, Posadas O, Mishra A, Liu D, Beigel J, Rappuoli R, Tsang J, Golding H. Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus. Nature Medicine 2024, 30: 2771-2776. PMID: 39013430, DOI: 10.1038/s41591-024-03189-y.Peer-Reviewed Original ResearchCross-neutralizing antibodiesH5N1 vaccineNeutralizing antibody responsesVaccination of adultsDevelopment of effective vaccinesGlobal public health threatHPAI H5N1Influenza virusSeroconversion ratesH5N1Neutralizing antibodiesCross-reactive bindingPublic health threatLicensed vaccinesHemagglutination inhibitionPublic health priorityAntibody responseEffective vaccineHPAIVaccineAntibodiesDoseHealth priorityVirusHealth threat
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 ResearchRobust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children.
Manthiram K, Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, 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, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, Pittaluga S, Germain R, Apps R, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P. Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children. Research Square 2022 PMID: 35350206, PMCID: PMC8963700, DOI: 10.21203/rs.3.rs-1276578/v1.Peer-Reviewed Original Research