Matthew Mulè
Hospital ResidentCards
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Featured Publications
Integrating 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+ monocytesSingle-cell levelBiological insightsUnadjuvanted vaccineAS03-adjuvantedInfluenza vaccineResponse phenotypesCITE-seqInnate subsetsAdjuvant developmentHigh antibody respondersDay 1Antibody respondersLipopolysaccharide stimulationVaccineCorrelation networkHuman populationNormalizing 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 variationMultigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation
Mulé M, Mannis G, Wood B, Radich J, Hwang J, Ramos N, Andreadis C, Damon L, Logan A, Martin T, Hourigan C. Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation. Transplantation And Cellular Therapy 2016, 22: 1974-1982. PMID: 27544285, PMCID: PMC5072749, DOI: 10.1016/j.bbmt.2016.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutograftsFemaleFlow CytometryGenes, Wilms TumorHematopoietic Stem Cell TransplantationHumansLeukapheresisLeukemia, Myeloid, AcuteMaleMiddle AgedNeoplasm, ResidualPolymerase Chain ReactionPredictive Value of TestsRecurrenceRetrospective StudiesRisk AssessmentSpecimen HandlingTransplantation, AutologousYoung AdultConceptsMeasurable residual diseaseAcute myeloid leukemiaMultiparameter flow cytometryPeripheral blood progenitor cellsAutologous hematopoietic cell transplantationAuto-HCTHematopoietic cell transplantationCell transplantationRQ-PCRAdult patientsAML MRD testingAutologous peripheral blood progenitor cellRelapse predictionCD34+ cell doseMeasurable residual disease testingMultivariate analysisMultivariate analysis of clinical variablesAcute myeloid leukemia patientsPredictive valueAnalysis of clinical variablesMRD-negative cohortMRD-negative patientsMRD-positive patientsRelapse risk stratificationBlood progenitor cellsIron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Hanson A, Mulè M, Ruffieux H, Mescia F, Bergamaschi L, Pelly V, Turner L, Kotagiri P, Göttgens B, Hess C, Gleadall N, Bradley J, Nathan J, Lyons P, Drakesmith H, Smith K. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nature Immunology 2024, 25: 471-482. PMID: 38429458, PMCID: PMC10907301, DOI: 10.1038/s41590-024-01754-8.Peer-Reviewed Original ResearchConceptsStress erythropoiesisNumbers of dendritic cellsLow serum ironSARS-CoV-2Long-term outcomesWeek of diseaseIncreased iron demandOutcomes of COVID-19SARS-CoV-2 infectionCOVID-19 symptom onsetCOVID-19 severityDendritic cellsPersistent symptomatologyMonth 1Serum ironProliferating lymphocytesIron homeostasisUnresolved inflammationSymptom onsetPersistent symptomsHospitalized patientsDysregulated erythropoiesisInflammatory disequilibriumLong-term outcomes of COVID-19Iron homeostasis gene expressionBroad 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 response
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, PMCID: PMC11949244, 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 factorsH5N1DaysAS03
2022
Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Hagan T, Gerritsen B, Tomalin LE, Fourati S, Mulè MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Sékaly R, Kleinstein S, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses. Nature Immunology 2022, 23: 1788-1798. PMID: 36316475, PMCID: PMC9869360, DOI: 10.1038/s41590-022-01328-6.Peer-Reviewed Original ResearchConceptsAntibody responseDay 1Vaccine-induced antibodiesYellow fever vaccineHuman immune responseMechanisms of immunityB cell activationTranscriptional atlasFever vaccineDifferent vaccinesSystems vaccinologyImmune responseMost vaccinesDay 7Cell activationInnate immunityVaccineVaccinationImmunityCommon predictorsMolecular signaturesResponsePlasmablastsInterferonAntibodiesPan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvantThe Immune Signatures data resource, a compendium of systems vaccinology datasets
Diray-Arce J, Miller HER, Henrich E, Gerritsen B, Mulè MP, Fourati S, Gygi J, Hagan T, Tomalin L, Rychkov D, Kazmin D, Chawla DG, Meng H, Dunn P, Campbell J, Sarwal M, Tsang J, Levy O, Pulendran B, Sekaly R, Floratos A, Gottardo R, Kleinstein S, Suárez-Fariñas M. The Immune Signatures data resource, a compendium of systems vaccinology datasets. Scientific Data 2022, 9: 635. PMID: 36266291, PMCID: PMC9584267, DOI: 10.1038/s41597-022-01714-7.Peer-Reviewed Original ResearchConceptsHuman Immunology Project ConsortiumDifferent vaccinesCost-effective public health interventionsGene Expression OmnibusInfection-induced morbiditySystems immunology approachPublic health interventionsMultiple relevant studiesVaccine responsesHealth interventionsVaccineRelevant studiesVaccine discoveryUnderstanding of mechanismsMolecular signaturesImmPortSystems immunologyImmunologyStudy dataTraditional immunologyMorbidityCohortImmunogenicityMortalityRelease
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, Han K, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS, Consortium N, Abers M, Apps R, Bosticardo M, Milanez-Almeida P, Mulè M, Shaw E, Zhang Y, Clinicians C, Castelli F, Muiesan M, Tomasoni G, Scolari F, Tucci A, Rossi C, Su H, Kuhns D, Cohen J, Notarangelo L, Tsang J. 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