2024
Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome
Wang S, Xiong Y, Jang M, Park K, Donahue M, Velez J, Jin J, Jiang Y. Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome. Molecular Therapy 2024, 32: 2662-2675. PMID: 38796700, DOI: 10.1016/j.ymthe.2024.05.034.Peer-Reviewed Original ResearchPrader-Willi syndromeEpigenetic therapyMouse modelChromosome 15q11-q13 regionPWS mouse modelFirst-in-class inhibitorEfficacy of oral administrationPoor oral bioavailabilityPotential epigenetic therapiesReduction of H3K9me2Paternally expressed genesOral bioavailabilityIntraperitoneal routeOral administrationPerinatal lethalityTherapeutic benefitBrain penetrationMolecular efficacyPatient fibroblastsEpigenetic modulationGenomic disordersMaternal chromosomeBrain permeabilityLiver tissueCandidate genes
2023
Novel epigenetic molecular therapies for imprinting disorders
Wang S, Jiang Y. Novel epigenetic molecular therapies for imprinting disorders. Molecular Psychiatry 2023, 28: 3182-3193. PMID: 37626134, PMCID: PMC10618104, DOI: 10.1038/s41380-023-02208-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsActive alleleImprinting disordersMolecular mechanismsGenome editing approachesEpigenetic-based therapiesUnique molecular mechanismGenomic imprinting disordersImprinted genesGenome editingMolecular approachesEditing approachesInactive allelesNew therapeutic strategiesAllelesSmall moleculesMolecular therapyTherapeutic strategiesAbnormal kynurenine level contributes to the pathological bone features of ankylosing spondylitis
Jeon C, Jang Y, Lee S, Weon S, Park H, Lee S, Oh Y, Choi S, Wang S, Kim T, Sung I, Jo S. Abnormal kynurenine level contributes to the pathological bone features of ankylosing spondylitis. International Immunopharmacology 2023, 118: 110132. PMID: 37023698, DOI: 10.1016/j.intimp.2023.110132.Peer-Reviewed Original ResearchConceptsModified Stoke Ankylosing Spondylitis Spinal ScoreKyn levelsMouse osteoclast precursorsSera levelsAnkylosing spondylitisStoke Ankylosing Spondylitis Spinal ScoreAS groupDisease activity of ASKyn treatmentOsteoclast formationOsteoclast precursorsTRAP-positive osteoclast formationOsteoblast differentiationSystemic bone lossRANKL-mediated osteoclast differentiationBone formationBone mineralizationCell proliferationFeatures of ankylosing spondylitisOsteoclast differentiation markersRANKL-mediated osteoclastogenesisMRNA expression markersActivity of ASAlkaline phosphateKynurenine levels
2022
Epigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders
Wang S, Jiang Y. Epigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders. 2022, 405-426. DOI: 10.1007/978-3-030-94475-9_17.ChaptersEpigenome-wide association studiesAbnormal DNA methylationDNA methylationHistone modificationsTissue-specific patternsNeurodevelopmental disordersEpigenetic regulationEpigenetic epidemiologyEmbryonic developmentEpigenetic dysregulationGenetic lociEpigenetic reprogramingAssociation studiesMethylationRecent technical advancesEnvironmental factorsRegion analysisEpimutationsReprogramingEtiology of NDDIntellectual disabilityLociTechnical advancesAllelesRegulation
2021
LGI1 governs neuritin-mediated resilience to chronic stress
Lee S, Kim N, Choi M, Ko S, Wang S, Jo H, Seo J, Kim Y, Kim H, Lee H, Kim J, Son H. LGI1 governs neuritin-mediated resilience to chronic stress. Neurobiology Of Stress 2021, 15: 100373. PMID: 34401409, PMCID: PMC8350063, DOI: 10.1016/j.ynstr.2021.100373.Peer-Reviewed Original ResearchLeucine-rich glioma-inactivated protein 1Chronic unpredictable stressLGI1 expressionAntidepressant-like behaviorHippocampus of miceHistone deacetylase 5 (HDAC5) phosphorylationDevelopment of CNSInsulin receptor inhibitorNeuronal atrophyFlox/Unpredictable stressReceptor inhibitorsChronic stressNeuritinHDAC5 phosphorylationProtein 1Pathological depressionMetastasis suppressorEndogenous proteinsNeurite outgrowthMiceDepressionStress resilienceCritical roleExpression
2019
Downregulation of SIRT2 by Chronic Stress Reduces Expression of Synaptic Plasticity-related Genes through the Upregulation of Ehmt2
Wang S, Ko S, Jo S, Jo H, Han J, Kim Y, Son H. Downregulation of SIRT2 by Chronic Stress Reduces Expression of Synaptic Plasticity-related Genes through the Upregulation of Ehmt2. Experimental Neurobiology 2019, 28: 537-546. PMID: 31495082, PMCID: PMC6751865, DOI: 10.5607/en.2019.28.4.537.Peer-Reviewed Original ResearchPlasticity-related genesSynaptic plasticity-related genesLysine N-methyltransferase 2Cellular oxidative stress responseDepression-like behaviorSilent information regulator 2Oxidative stress responseDownregulation of SIRT2SIRT2 expressionTranscriptional silencingKnockdown of SIRT2Protein stabilityRegulator 2Target proteinsChronic stressStress responseHippocampus-dependent cognitive functionDependent deacetylaseGenesBiochemical analysisStress-induced decreaseSIRT2Reduces ExpressionExpressionMood disordersPotential of Epigenetic Therapy for Prader-Willi Syndrome
Wang SE, Jiang YH. Potential of Epigenetic Therapy for Prader-Willi Syndrome. Trends In Pharmacological Sciences 2019, 40: 605-608. PMID: 31353046, DOI: 10.1016/j.tips.2019.07.002.Peer-Reviewed Original ResearchEpigenetic therapy of Prader–Willi syndrome
Kim Y, Wang SE, Jiang YH. Epigenetic therapy of Prader–Willi syndrome. Translational Research 2019, 208: 105-118. PMID: 30904443, PMCID: PMC6527448, DOI: 10.1016/j.trsl.2019.02.012.Peer-Reviewed Original ResearchConceptsPWS mouse modelEpigenetic-based therapiesMaternal chromosomesImprinted gene regulationEHMT2/G9aLysine 9 methyltransferasePatient-derived fibroblastsPrader-Willi syndromeGene regulationMethyltransferase SETDB1Epigenetic mechanismsSmall molecule librariesPWS genesHigh-content screeningSame genePerinatal lethalityEpigenetic therapyFusion proteinMolecular mechanismsG9a inhibitorChromosomesSNORD116 clusterGenesMolecular defectsPatient iPSCTransient receptor potential melastatin 2 governs stress-induced depressive-like behaviors
Ko SY, Wang SE, Lee HK, Jo S, Han J, Lee SH, Choi M, Jo HR, Seo JY, Jung SJ, Son H. Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 1770-1775. PMID: 30642955, PMCID: PMC6358711, DOI: 10.1073/pnas.1814335116.Peer-Reviewed Original ResearchConceptsMajor depressive disorderChronic unpredictable stressReactive oxygen speciesStress-induced depressive-like behaviorTransient receptor potential melastatin 2Antidepressant-like behaviorDepressive-like behaviorStress-induced depressionEnvironmental risk factorsHippocampal tissue samplesHistone deacetylase 5Risk factorsDepressive disorderUnpredictable stressPermeable cation channelSynapsin 1Animal modelsType 2Calpain activationSynaptic functionChronic stressMRNA expressionCation channelsTissue samplesPossible targets
2018
Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis
Jo S, Han J, Lee YL, Yoon S, Lee J, Wang SE, Kim T. Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis. International Journal Of Rheumatic Diseases 2018, 22: 252-261. PMID: 30415492, DOI: 10.1111/1756-185x.13419.Peer-Reviewed Original ResearchConceptsHealthy controlsPrimary CTAS patientsAge-matched healthy controlsRheumatoid arthritis patientsAlkaline phosphatase levelsPossible therapeutic targetOsteoblast differentiationAlkaline phosphataseALP activityRunt-related transcription factor 2RA groupArthritis patientsMale patientsPrimary diseaseSpinal ankylosisRegulation of osteoblastSerum ALPPhosphatase levelsTherapeutic targetALP levelsTranscription factor 2Master transcriptional factorPatientsOsteoblastic activityIL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis
Jo S, Wang SE, Lee YL, Kang S, Lee B, Han J, Sung IH, Park YS, Bae SC, Kim TH. IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis. Arthritis Research & Therapy 2018, 20: 115. PMID: 29880011, PMCID: PMC5992730, DOI: 10.1186/s13075-018-1582-3.Peer-Reviewed Original ResearchConceptsIL-17AJAK2/STAT3Rheumatoid arthritisHealthy controlsExogenous IL-17AIL-12/23 p40Abnormal bone formationNew rational therapiesStimulus-induced increaseALP activityBone tissue samplesPrimary BdCsControl patientsExtensive inflammationAS pathogenesisBony ankylosisP40 levelsSpinal diseaseFacet jointsRational therapySynovial fluidPatientsPrimary bone-derived cellsBone-derived cellsJAK2 inhibitorsCapsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice
Wang SE, Ko SY, Kim YS, Jo S, Lee SH, Jung SJ, Son H. Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice. Experimental & Molecular Medicine 2018, 50: e455-e455. PMID: 29520110, PMCID: PMC5898893, DOI: 10.1038/emm.2017.289.Peer-Reviewed Original ResearchConceptsTransient receptor potential vanilloid 1Histone deacetylase 2Synapsin IAgonist of TRPV1Synaptic plasticityRole of HDAC2GluR2 promoterCapsaicin treatmentVanilloid 1Neuronal maturationMouse hippocampusTRPV1 activityHippocampal knockdownChromatin remodelingTranscriptional regulationSynaptic moleculesCapsaicinMolecular linkGene expressionMicePresent studyDetrimental effectsRegulationSynaptophysinHippocampus
2017
Oleanolic Acid Promotes Neuronal Differentiation and Histone Deacetylase 5 Phosphorylation in Rat Hippocampal Neurons
Jo HR, Wang SE, Kim YS, Lee CH, Son H. Oleanolic Acid Promotes Neuronal Differentiation and Histone Deacetylase 5 Phosphorylation in Rat Hippocampal Neurons. Molecules And Cells 2017, 40: 485-494. PMID: 28681592, PMCID: PMC5547218, DOI: 10.14348/molcells.2017.0034.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsCell DifferentiationCell NucleusDendritic SpinesGene Expression RegulationHippocampusHistone DeacetylasesMEF2 Transcription FactorsNeural Stem CellsNeuritesNeuronsOleanolic AcidPhosphorylationProtein Kinase CRats, Sprague-DawleySubcellular FractionsSynapsesConceptsRat hippocampal neural progenitor cellsEffects of OAHippocampal neural progenitor cellsNeuronal differentiationOA derivativesOleanolic acidHDAC5 phosphorylationHistone deacetylase 5 (HDAC5) phosphorylationRat hippocampal neuronsNeural progenitor cellsPromotes Neuronal DifferentiationHistone deacetylase 5Neurotrophic effectsHippocampal neuronsNeurological drugsProgenitor cellsNeural differentiationNeuronsPresent studyTarget genesExpressionFurther researchGene expressionPhosphorylationDifferentiationTRPV1 Regulates Stress Responses through HDAC2
Wang SE, Ko SY, Jo S, Choi M, Lee SH, Jo HR, Seo JY, Lee SH, Kim YS, Jung SJ, Son H. TRPV1 Regulates Stress Responses through HDAC2. Cell Reports 2017, 19: 401-412. PMID: 28402861, DOI: 10.1016/j.celrep.2017.03.050.Peer-Reviewed Original ResearchConceptsTransient receptor potential vanilloid 1Neuroplasticity-related moleculesTRPV1-deficient miceChronic unpredictable stressNon-selective cation channelsStress-induced behaviorsHDAC2 overexpressionVanilloid 1Control micePain sensationUnpredictable stressTRPV1 activityHippocampal knockdownNeurotransmission systemsGlucocorticoid receptorBehavioral effectsCation channelsMiceStress responseHDAC2BrainSimilar effectsMolecular linkCellular levelResponse
2015
Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats
Choi M, Lee SH, Wang SE, Ko SY, Song M, Choi JS, Kim YS, Duman RS, Son H. Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 15755-15760. PMID: 26647181, PMCID: PMC4697416, DOI: 10.1073/pnas.1513913112.Peer-Reviewed Original ResearchConceptsHistone deacetylase 5Myocyte enhancer factor 2MEF2 target genesNuclear exportTarget genesTranscriptional activityPhosphorylation-dependent nuclear exportPhosphorylation-defective mutantProtein kinase DHistone deacetylase 5 (HDAC5) phosphorylationMEF2 transcriptional activityAntidepressant-like effectsCalcium/calmodulin kinase IICalmodulin kinase IIKinase DKinase IIMolecular mechanismsNovel roleRapid antidepressant-like effectsDependent pathwayAction of ketamineFactor 2Rat hippocampal neuronsGenesHippocampal knockdown
2014
Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Rats
Choi M, Wang SE, Ko SY, Kang HJ, Chae SY, Lee SH, Kim YS, Duman RS, Son H. Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Rats. PLOS ONE 2014, 9: e109253. PMID: 25340772, PMCID: PMC4207676, DOI: 10.1371/journal.pone.0109253.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalCells, CulturedDendritic SpinesDependovirusDepressionGATA1 Transcription FactorGATA2 Transcription FactorGene Expression RegulationGreen Fluorescent ProteinsHippocampusHumansMaleRats, Sprague-DawleyRats, TransgenicRNA, Small InterferingSynapsesTranscription, GeneticConceptsSynapse-related genesSpine numberDentate gyrusDepressive behaviorDorsal hippocampusHippocampal neuronsSpine formationViral expressionDepressive-like deficitsSpine synapse densitySynapse-related gene expressionEffects of adenoRat hippocampal neuronsViral-mediated expressionModel of depressionSwim testSynapse densityDendritic outgrowthAdult brainHippocampusNeuronal differentiationDendrite branchingShRNA knockdownGATA-2Helplessness modelCarbamylated erythropoietin promotes neurite outgrowth and neuronal spine formation in association with CBP/p300
Choi M, Ko SY, Lee IY, Wang SE, Lee SH, Oh DH, Kim YS, Son H. Carbamylated erythropoietin promotes neurite outgrowth and neuronal spine formation in association with CBP/p300. Biochemical And Biophysical Research Communications 2014, 446: 79-84. PMID: 24607903, DOI: 10.1016/j.bbrc.2014.02.066.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCells, CulturedDisks Large Homolog 4 ProteinE1A-Associated p300 ProteinEpigenesis, GeneticErythropoietinIntracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMembrane ProteinsNerve Tissue ProteinsNeuritesNeurogenesisNeuronsPhosphorylationProto-Oncogene Proteins c-aktRatsSTAT3 Transcription FactorTranscriptional ActivationTumor Suppressor Protein p53Up-RegulationConceptsNeuronal differentiationNeuronal spine formationCBP/p300E1A-binding proteinSpine formationTreatment of cellsEpigenetic modificationsTranscription factorsSubsequent transactivationTarget genesTransactivation activityGene expressionMolecular mechanismsImportant medical implicationsLength of neuritesP53 acetylationNeurite outgrowthGrowth-associated protein 43TransactivationAcetylationMedical implicationsDifferentiationProtein 43Spine densityNeuropsychiatric disorders