Featured Publications
A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells
Axisa P, Yoshida T, Lucca L, Kasler H, Lincoln M, Pham G, Del Priore D, Carpier J, Lucas C, Verdin E, Sumida T, Hafler D. A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells. Science Translational Medicine 2022, 14: eabl3651. PMID: 36516268, DOI: 10.1126/scitranslmed.abl3651.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesDisease Models, AnimalGenome-Wide Association StudyHistone DeacetylasesHumansMiceMultiple SclerosisT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalitisRegulatory T cellsHistone deacetylase 7Multiple sclerosisT cellsMouse modelFunction of Foxp3CD4 T cellsHigher suppressive capacityVivo modelingAutoimmune encephalitisEAE severityImmunosuppressive subsetAutoimmune diseasesImmunomodulatory roleSuppressive capacityImmune cellsDisease onsetDistinct molecular classesSusceptibility lociGenetic susceptibility lociSingle-cell RNA sequencingDisease riskPatient samplesProtective variants
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
2016
Activation of endothelial β-catenin signaling induces heart failure
Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I. Activation of endothelial β-catenin signaling induces heart failure. Scientific Reports 2016, 6: 25009. PMID: 27146149, PMCID: PMC4857119, DOI: 10.1038/srep25009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninDisease Models, AnimalEndothelial CellsErbB ReceptorsHeart FailureMiceNeuregulin-1Survival AnalysisWnt Signaling PathwayConceptsWnt/β-cateninHeart failureCardiac dysfunctionCa miceEndothelial cellsΒ-cateninEndothelial β-cateninProgressive cardiac dysfunctionCardiac endothelial cellsDegeneration of mitochondriaArterial endothelial cellsNeuregulin-ErbB signalingNeuregulin proteinΒ-catenin-dependent canonical WntEndothelial expressionIschemic diseasesTherapeutic targetDysfunctionMiceSustained activationFunction mutationsNeuregulin-ErbBT-tubulesCanonical WntConditional gain
2015
Wnt/&bgr;-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O
Okada K, Naito AT, Higo T, Nakagawa A, Shibamoto M, Sakai T, Hashimoto A, Kuramoto Y, Sumida T, Nomura S, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Morimoto S, Sakata Y, Shiojima I, Komuro I. Wnt/&bgr;-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O. Circulation Heart Failure 2015, 8: 799-808. PMID: 26038536, DOI: 10.1161/circheartfailure.114.001958.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCardiomyopathy, DilatedCell LineComplement C1qDisease Models, AnimalForkhead Box Protein O1Forkhead Transcription FactorsMice, TransgenicMuscle FatigueMuscle Fibers, SkeletalMuscle, SkeletalMuscular DiseasesRNA InterferenceTransfectionWnt Signaling PathwayWnt3A ProteinConceptsChronic heart failureFiber type shiftFatigable fibersSkeletal myopathyActivation of WntHeart failureModel miceCardiomyopathy miceSkeletal muscleNovel therapeutic targetMediator β-cateninType IIB fibersControl miceType shiftC2C12 cellsTherapeutic targetSignaling contributesComplement C1qMyopathyMiceCritical roleIIB fibersForkhead box OΒ-cateninFoxO1 activity
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 p53Ubiquitin-Protein LigasesUbiquitinationVentricular 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