Featured Publications
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactionsComplement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling
Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I. Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling. Nature Communications 2015, 6: 6241. PMID: 25716000, PMCID: PMC4351572, DOI: 10.1038/ncomms7241.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsProliferation of VSMCsArterial remodellingΒ-catenin signalingΒ-cateninComplement C1qBlood pressure elevationEnd-organ damageNovel therapeutic targetSmooth muscle cellsMacrophage depletionImmune cellsPrecise molecular mechanismsTherapeutic targetStructural remodellingMuscle cellsRemodellingHypertensionArteriosclerosisComplement C1ActivationC1qMolecular mechanismsSignalingGene deletion
2024
Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation
Hanin A, Comi M, Sumida T, Hafler D. Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation. Life Science Alliance 2024, 7: e202402890. PMID: 39366761, PMCID: PMC11452476, DOI: 10.26508/lsa.202402890.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cellsEffector/memory cellsCentral nervous system milieuT cell environmentCD4 T cellsIFNG mRNA expressionCXCR3<sup>+</sup> cellsT cell homeostasisInhibition of SGK1Targeting lipid pathwaysMaintenance of immune surveillanceSerum/glucocorticoid-regulated kinaseImmune surveillanceHealthy donorsCytotoxic capacityEffector responsesInflammatory conditionsSGK1 activityMRNA expressionNervous systemSGK1Metabolic conditionsLipid pathwaysTissue adaptation
2019
Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction
Shibamoto M, Higo T, Naito AT, Nakagawa A, Sumida T, Okada K, Sakai T, Kuramoto Y, Yamaguchi T, Ito M, Masumura Y, Higo S, Lee JK, Hikoso S, Komuro I, Sakata Y. Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction. International Heart Journal 2019, 60: 944-957. PMID: 31257341, DOI: 10.1536/ihj.18-701.Peer-Reviewed Original ResearchConceptsCellular senescenceDNA damage response systemDNA damage responseCardiac fibroblastsDDR activationDamage responseMolecular mechanismsSenescenceGene deletionJuxtacrine mannerProliferation of CFsCardiac fibrosisCF proliferationProliferationCardiac remodelingActivationTissue fibrosisRemodelingImportant roleTherapeutic strategiesRoleRecent reportsDeletionRegulationATM gene deletionAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2018
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure
Nomura S, Satoh M, Fujita T, Higo T, Sumida T, Ko T, Yamaguchi T, Tobita T, Naito AT, Ito M, Fujita K, Harada M, Toko H, Kobayashi Y, Ito K, Takimoto E, Akazawa H, Morita H, Aburatani H, Komuro I. Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure. Nature Communications 2018, 9: 4435. PMID: 30375404, PMCID: PMC6207673, DOI: 10.1038/s41467-018-06639-7.Peer-Reviewed Original ResearchConceptsCardiac hypertrophyCardiomyocyte remodelingGene programHeart failurePressure overloadMorphological hypertrophyHeart functionHypertrophyP53 deletionEarly hypertrophyFunctional signaturesFunctional phenotypeLate hypertrophyP53 signalingTranscriptional signatureProgram activationMitochondrial inhibitionUnderlying mechanismCardiomyocyte identityCardiomyocytesMitochondrial activationRemodelingFailureTranscriptional programsActivationPhenotypic Screening Using Patient-Derived Induced Pluripotent Stem Cells Identified Pyr3 as a Candidate Compound for the Treatment of Infantile Hypertrophic Cardiomyopathy
Sakai T, Naito AT, Kuramoto Y, Ito M, Okada K, Higo T, Nakagawa A, Shibamoto M, Yamaguchi T, Sumida T, Nomura S, Umezawa A, Miyagawa S, Sawa Y, Morita H, Lee JK, Shiojima I, Sakata Y, Komuro I. Phenotypic Screening Using Patient-Derived Induced Pluripotent Stem Cells Identified Pyr3 as a Candidate Compound for the Treatment of Infantile Hypertrophic Cardiomyopathy. International Heart Journal 2018, 59: 17-730. PMID: 30101858, DOI: 10.1536/ihj.17-730.Peer-Reviewed Original ResearchConceptsDiastolic intracellular calcium concentrationInfantile hypertrophic cardiomyopathyHypertrophic cardiomyopathyIntracellular calcium concentrationHCM patientsIPSC-CMsInduced pluripotent stem cellsNoonan syndromeCalcium concentrationIdiopathic hypertrophic cardiomyopathyPatient-derived induced pluripotent stem cellsStem cellsPluripotent stem cellsHealthy subjectsPatientsChannel inhibitorsPhenotypic screeningPyr3Genetic disordersDisease-related phenotypesCardiomyopathySyndromeCandidate compoundsPresent studyTreatment
2015
Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression
Yabumoto C, Akazawa H, Yamamoto R, Yano M, Kudo-Sakamoto Y, Sumida T, Kamo T, Yagi H, Shimizu Y, Saga-Kamo A, Naito AT, Oka T, Lee JK, Suzuki J, Sakata Y, Uejima E, Komuro I. Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression. Scientific Reports 2015, 5: 14453. PMID: 26571361, PMCID: PMC4585890, DOI: 10.1038/srep14453.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, TopicalAgingAngiotensin II Type 1 Receptor BlockersAnimalsAxin ProteinBiphenyl CompoundsCell LineComplement C1qDown-RegulationImmunohistochemistryIrbesartanMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMuscle, SkeletalPAX7 Transcription FactorReceptor, Angiotensin, Type 1RegenerationTetrazolesWnt Signaling PathwayConceptsC1q expressionReceptor blockadeAge-related declineAngiotensin II receptor blockadeAT1 receptor blocker irbesartanAngiotensin II type 1 receptorII type 1 receptorAT1 receptor blockadeFunctional muscle recoveryII receptor blockadeSkeletal muscleReceptor blocker irbesartanType 1 receptorWnt/β-catenin pathwaySkeletal muscle functionWnt/β-catenin signalingMuscle regenerationΒ-catenin pathwayCultured macrophage cellsΒ-catenin signalingAT1 receptorMuscle recoveryM2 polarizationMuscle functionTopical administrationA Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling
Nakayama A, Morita H, Nakao T, Yamaguchi T, Sumida T, Ikeda Y, Kumagai H, Motozawa Y, Takahashi T, Imaizumi A, Hashimoto T, Nagai R, Komuro I. A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling. PLOS ONE 2015, 10: e0137106. PMID: 26327560, PMCID: PMC4556625, DOI: 10.1371/journal.pone.0137106.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAntioxidantsAtrial Natriuretic FactorConnective Tissue Growth FactorDietFibroblastsFibrosisFlavonoidsFoodHeartHydrogen PeroxideHypertrophyLuteolinMaleMyocardiumOxidative StressPhosphorylationRatsRats, Sprague-DawleySignal TransductionTransforming Growth Factor beta1Ventricular RemodelingConceptsCardiac remodelingAng IIOral pretreatmentII-Induced Cardiac RemodelingOxidative stressCultured rat cardiac fibroblastsRat cardiac fibroblastsPhosphorylation of JNKHyperoxidative stateAntifibrotic effectsCardiac fibrosisCardiac functionLuteolin pretreatmentTGFβ1 expressionCardiac fibroblastsPotent antioxidantHerbal extractsProtective actionCardiac tissueRemodelingExpression levelsGene expression levelsDietPretreatmentProtective properties
2010
Promotion of CHIP-Mediated p53 Degradation Protects the Heart From Ischemic Injury
Naito AT, Okada S, Minamino T, Iwanaga K, Liu ML, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I. Promotion of CHIP-Mediated p53 Degradation Protects the Heart From Ischemic Injury. Circulation Research 2010, 106: 1692-1702. PMID: 20413784, DOI: 10.1161/circresaha.109.214346.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisBase SequenceBenzoquinonesCell HypoxiaChlorocebus aethiopsCOS CellsDisease Models, AnimalGenetic TherapyHSP90 Heat-Shock ProteinsHumansHypoxia-Inducible Factor 1, alpha SubunitLactams, MacrocyclicMaleMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMutationMyocardial InfarctionMyocytes, CardiacPromoter Regions, GeneticProteasome Endopeptidase ComplexProtein Processing, Post-TranslationalRatsRats, WistarRNA InterferenceTranscriptional ActivationTumor Suppressor Protein p53UbiquitinationUbiquitin-Protein LigasesVentricular RemodelingConceptsMyocardial infarctionP53 accumulationCardiomyocyte apoptosisCoronary heart diseaseNumber of patientsNovel therapeutic strategiesP53 degradationApoptosis of cardiomyocytesHeat shock proteinsHeart failureIschemic injuryCardioprotective effectsVentricular remodelingCHIP overexpressionHeart diseaseInfarctionTherapeutic strategiesProteasomal degradationMyocardial apoptosisAmount of p53Molecular mechanismsShock proteinsP53 antagonistP53 accumulatesProtein levels