2025
Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs
Lyu W, Li Y, Yao A, Tan Q, Zhang R, Zhao J, Guo K, Jiang Y, Tian R, Zhang Y. Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs. Translational Psychiatry 2025, 15: 76. PMID: 40050270, DOI: 10.1038/s41398-025-03296-5.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderMutant damsWild-typeMaternal behaviorASD risk genesLicking behaviorAbundant scaffolding proteinImpaired social interactionEffects of oxytocinCRISPR/Cas9 methodologyRisk genesMutant dogsNursing frequencyOXT treatmentBehavioral deficitsRepetitive behaviorsPotential therapeutic strategySpectrum disorderEndothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling
Kim Y, Kim M, Kim S, Lee R, Ujihara Y, Marquez-Wilkins E, Jiang Y, Yang E, Kim H, Lee C, Park C, Kim I. Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling. Nature Communications 2025, 16: 1407. PMID: 39915488, PMCID: PMC11802743, DOI: 10.1038/s41467-025-56720-1.Peer-Reviewed Original ResearchConceptsBlood-brain barrierNeuronal excitabilityB-cateninBarrier functionMouse blood-brain barrierReduced neuronal excitabilityMale mutant miceBlood-brain barrier permeabilityBrain endothelial cellsAutism spectrum disorderNeonatal micePotential therapeutic targetASD risk genesMutant miceTight junctionsImpaired sociabilityPathogenic mechanismsBrain parenchymaEndothelial cellsTherapeutic targetASD pathogenesisSHANK3Adult ageDisabling conditionMice
2024
Impaired tactile processing in autism-associated Shank3 mutant dogs: neural mechanism and intervention
Shi Q, Wu L, Ren B, Guo K, Jiang Y, Zhang Y, Hu L. Impaired tactile processing in autism-associated Shank3 mutant dogs: neural mechanism and intervention. Science Bulletin 2024, 70: 483-487. PMID: 39294081, DOI: 10.1016/j.scib.2024.09.011.Peer-Reviewed Original ResearchProximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions
Gao Y, Shonai D, Trn M, Zhao J, Soderblom E, Garcia-Moreno S, Gersbach C, Wetsel W, Dawson G, Velmeshev D, Jiang Y, Sloofman L, Buxbaum J, Soderling S. Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions. Nature Communications 2024, 15: 6801. PMID: 39122707, PMCID: PMC11316102, DOI: 10.1038/s41467-024-51037-x.Peer-Reviewed Original ResearchConceptsSpatial proteomicsRisk genesHigh-confidence risk genesRegulation of expressionAutism risk genesGenetic interactionsProximity proteomicsHuman genesEndogenous proteomesProtein complexesCellular functionsNative proteomeProteomicsPhenotypic modifiersRisk allelesRelevant to autismGenesFunctional interactionsGenetic riskProteinMouse brainMouse model of autismCellular driversProximity interactionsMouse modelTranscriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes
Lu X, Ni P, Suarez-Meade P, Ma Y, Forrest E, Wang G, Wang Y, Quiñones-Hinojosa A, Gerstein M, Jiang Y. Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes. Cell Reports 2024, 43: 114376. PMID: 38900637, PMCID: PMC11328446, DOI: 10.1016/j.celrep.2024.114376.Peer-Reviewed Original ResearchSHANK family genesFamily genesLong-read sequencingCDNA captureTranscript structureDeleterious variantsGenomic studiesAbundant mRNAsTranscriptional dysregulationStochastic transcriptionStudies of neuropsychiatric disordersCausative genesTranscriptional profilesTranscriptional determinantsTranscriptomePostmortem brain tissueAutism spectrum disorderShank3 transcriptsTranscriptionGenesGenomeSHANK3Neuropsychiatric disordersSpectrum disorderAutism modelNewly 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, PMCID: PMC11405540, 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 genesNovel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders
Lu X, Ng K, Pinto e Vairo F, Collins J, Cohn R, Riley K, Agre K, Gavrilova R, Klee E, Rosenfeld J, Jiang Y. Novel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders. European Journal Of Human Genetics 2024, 32: 879-883. PMID: 38702431, PMCID: PMC11219747, DOI: 10.1038/s41431-024-01576-0.Peer-Reviewed Original ResearchProtein-truncating variantsSyndromic neurodevelopmental disorderGenomic studiesChromatin-modifying enzymesAcetylation of histone H4Neurodevelopmental disordersLysine 34Histone 2BMono-ubiquitinationLysine 16Epigenetic machineryGenomic evaluationMSL2Exome sequencingHistone H4Epigenetic regulationModifying enzymesEpigenetic genesFunctional importanceGenesChromatinLysineDevelopmental disordersDysmorphic faceVariantsImpaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs
Zhu F, Shi Q, Jiang Y, Zhang Y, Zhao H. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Molecular Autism 2024, 15: 9. PMID: 38297387, PMCID: PMC10829216, DOI: 10.1186/s13229-024-00587-4.Peer-Reviewed Original ResearchConceptsPrefrontal cortexPyramidal neuronsSHANK3 mutationsPrefrontal cortex neuronal activityPrefrontal cortex pyramidal neuronsSocial behaviorBrain slicesPrefrontal cortex's roleSynaptic transmissionPrefrontal cortex layersStudy social cognitionAutism spectrum disorderAutism-like behaviorsDendritic spine morphologyReduced dendritic complexitySocial cognitionSocial impairmentBehavioral alterationsNeural mechanismsExcitatory synaptic transmissionMutant rodent modelsHeightened anxietySpectrum disorderSpine densityImpaired synaptic functionPatterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages
DiAdamo A, Chai H, Chong M, Wang G, Wen J, Jiang Y, Li P. Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages. Global Medical Genetics 2024, 11: 123-131. PMID: 38560483, PMCID: PMC10980555, DOI: 10.1055/s-0044-1785227.Peer-Reviewed Original ResearchRecurrent pregnancy lossProducts of conceptionAbnormal karyotypeConsecutive miscarriagesCase seriesCytogenomic abnormalitiesCA groupCytogenomic findingsRoutine cytogenetic analysisCopy number variantsMonosomy XNormal karyotypeRetrospective studyPregnancy lossCytogenetic analysisPathogenic variantsMiscarriageSA groupAneuploidyKaryotypeLethal variantWomenAbnormalitiesGenome sequenceAbstract Background
2023
Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing
Tian R, Li Y, Zhao H, Lyu W, Zhao J, Wang X, Lu H, Xu H, Ren W, Tan Q, Shi Q, Wang G, Zhang Y, Lai L, Mi J, Jiang Y, Zhang Y. Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing. Molecular Psychiatry 2023, 28: 3739-3750. PMID: 37848710, DOI: 10.1038/s41380-023-02276-9.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderNon-human primatesDog-human social interactionsPreclinical studiesBattery of behavioral assaysSocial behavior deficitsASD mouse modelsSocial interactionReduced social interactionCRISPR/Cas9 gene editingGenetic mutant miceNeural circuit mechanismsSocial withdrawalBehavioral findingsPsychiatric disordersBehavioral deficitsHeightened anxietyCanine modelSHANK3 mutationsSHANK3 geneCircuit mechanismsMutant miceMouse modelBehavioral assaysNovel 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 strategiesEstimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses
Peng G, Zhou Q, Chai H, Wen J, Zhao H, Taylor H, Jiang Y, Li P. Estimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses. Molecular Genetics & Genomic Medicine 2023, 11: e2181. PMID: 37013615, PMCID: PMC10422064, DOI: 10.1002/mgg3.2181.Peer-Reviewed Original ResearchConceptsGenomic disordersChromosome microarray analysisWilliams-Beuren syndromePathogenic copy number variantsPopulation genetic studiesWolf-Hirschhorn syndromeCopy number variantsDiGeorge syndromeMicroarray analysisMicroarray resultsChromosomal abnormalitiesGenetic studiesNumber variantsGenetic counselingSHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis
Zhang L, Bang S, He Q, Matsuda M, Luo X, Jiang Y, Ji R. SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis. Frontiers In Immunology 2023, 14: 1124356. PMID: 36845137, PMCID: PMC9944123, DOI: 10.3389/fimmu.2023.1124356.Peer-Reviewed Original ResearchConceptsVagal sensory neuronsNodose ganglionSensory neuronsSystemic inflammationBody temperatureDorsal root ganglion sensory neuronsSerum IL-6 levelsAuricular vagus nerve stimulationBasal core temperatureIL-6 levelsVagus nerve stimulationAutism spectrum disorderRole of Shank3Conditional knockout miceSynaptic scaffolding proteinsSepsis mortalityNerve stimulationExcessive inflammationHeat painInflammation dysregulationKO miceKnockout miceInflammationSHANK3 expressionNovel molecular mechanism
2022
Vitamin C epigenetically controls osteogenesis and bone mineralization
Thaler R, Khani F, Sturmlechner I, Dehghani SS, Denbeigh JM, Zhou X, Pichurin O, Dudakovic A, Jerez SS, Zhong J, Lee JH, Natarajan R, Kalajzic I, Jiang YH, Deyle DR, Paschalis EP, Misof BM, Ordog T, van Wijnen AJ. Vitamin C epigenetically controls osteogenesis and bone mineralization. Nature Communications 2022, 13: 5883. PMID: 36202795, PMCID: PMC9537512, DOI: 10.1038/s41467-022-32915-8.Peer-Reviewed Original ResearchConceptsSevere skeletal defectsBone-specific genesEpigenetic functionsChromatin accessibilityHistone demethylationDNA hydroxymethylationTranscriptional activityPro-osteogenic genesCell differentiationOsteogenic cell differentiationOsteogenic differentiationGenesSkeletal defectsBone phenotypeMurine boneOsteoblastogenesisDifferentiationKnockout miceGulo knockout miceVitamin C deficiencyTET1Collagen maturationPromoterDemethylationVitamin CA retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS resultsDisrupted Topological Organization of White Matter Network in Angelman Syndrome
Wei L, Du X, Yang Z, Ding M, Yang B, Wang J, Long S, Qiao Z, Jiang Y, Wang Y, Wang H. Disrupted Topological Organization of White Matter Network in Angelman Syndrome. Journal Of Magnetic Resonance Imaging 2022, 57: 1212-1221. PMID: 35856797, DOI: 10.1002/jmri.28360.Peer-Reviewed Original ResearchComparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains
Hong H, Zhao Z, Huang X, Guo C, Zhao H, Wang GD, Zhang YP, Zhao JP, Shi J, Wu QF, Jiang YH, Wang Y, Li LM, Du Z, Zhang YQ, Xiong Y. Comparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains. Molecular & Cellular Proteomics 2022, 21: 100261. PMID: 35738554, PMCID: PMC9304787, DOI: 10.1016/j.mcpro.2022.100261.Peer-Reviewed Original ResearchNeural circuit pathology driven by Shank3 mutation disrupts social behaviors
Kim S, Kim YE, Song I, Ujihara Y, Kim N, Jiang YH, Yin HH, Lee TH, Kim IH. Neural circuit pathology driven by Shank3 mutation disrupts social behaviors. Cell Reports 2022, 39: 110906. PMID: 35675770, PMCID: PMC9210496, DOI: 10.1016/j.celrep.2022.110906.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderAlters spine morphologyWild-type miceExcitatory-inhibitory balanceSocial dysfunctionHuman ASD patientsMultiple brain regionsSocial behaviorElevated neural activityCircuit pathologyPathogenic mechanismsSHANK3 mutationsCircuit inhibitionBrain regionsCircuit activationNeural network mechanismReduced sociabilitySpine morphologyCore symptomsASD patientsPrefrontal cortexMiceSHANK3 geneNeural activitySpectrum disorderEpigenetic 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 advancesAllelesRegulationThe microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder
Barish S, Senturk M, Schoch K, Minogue AL, Lopergolo D, Fallerini C, Harland J, Seemann JH, Stong N, Kranz PG, Kansagra S, Mikati MA, Jasien J, El-Dairi M, Galluzzi P, Acosta M, Adam M, Adams D, Agrawal P, Alejandro M, Alvey J, Amendola L, Andrews A, Ashley E, Azamian M, Bacino C, Bademci G, Baker E, Balasubramanyam A, Baldridge D, Bale J, Bamshad M, Barbouth D, Bayrak-Toydemir P, Beck A, Beggs A, Behrens E, Bejerano G, Bennet J, Berg-Rood B, Bernstein J, Berry G, Bican A, Bivona S, Blue E, Bohnsack J, Bonnenmann C, Bonner D, Botto L, Boyd B, Briere L, Brokamp E, Brown G, Burke E, Burrage L, Butte M, Byers P, Byrd W, Carey J, Carrasquillo O, Chang T, Chanprasert S, Chao H, Clark G, Coakley T, Cobban L, Cogan J, Coggins M, Cole F, Colley H, Cooper C, Cope H, Craigen W, Crouse A, Cunningham M, D'Souza P, Dai H, Dasari S, Davids M, Dayal J, Deardorff M, Dell'Angelica E, Dhar S, Dipple K, Doherty D, Dorrani N, Douine E, Draper D, Duncan L, Earl D, Eckstein D, Emrick L, Eng C, Esteves C, Estwick T, Falk M, Fernandez L, Ferreira C, Fieg E, Findley L, Fisher P, Fogel B, Forghani I, Fresard L, GahlIan-Glass W, Godfrey R, Golden-Grant K, Goldman A, Goldstein D, Grajewski A, Groden C, Gropman A, Gutierrez I, Hahn S, Hamid R, Hanchard N, Hassey K, Hayes N, High F, Hing A, Hisama F, Holm I, Hom J, Horike-Pyne M, Huang A, Huang Y, Isasi R, Jamal F, Jarvik G, Jarvik J, Jayadev S, Johnston J, Karaviti L, Kelley E, Kennedy J, Kiley D, Kohane I, Kohler J, Krakow D, Krasnewich D, Kravets E, Korrick S, Koziura M, Krier J, Lalani S, Lam B, Lam C, Lanpher B, Lanza I, Lau C, LeBlanc K, Lee B, Lee H, Levitt R, Lewis R, Lincoln S, Liu P, Liu X, Longo N, Loo S, Loscalzo J, Maas R, Macnamara E, MacRae C, Maduro V, Majcherska M, Mak B, Malicdan M, Mamounas L, Manolio T, Mao R, Maravilla K, Markello T, Marom R, Marth G, Martin B, Martin M, Martínez-Agosto J, Marwaha S, McCauley J, McConkie-Rosell A, McCormack C, McCray A, McGee E, Mefford H, Merritt J, Might M, Mirzaa G, Morava E, Moretti P, Morimoto M, Mulvihill J, Murdock D, Nakano-Okuno M, Nath A, Nelson S, Newman J, Nicholas S, Nickerson D, Nieves-Rodriguez S, Novacic D, Oglesbee D, Orengo J, Pace L, Pak S, Pallais J, Palmer C, Papp J, Parker N, Phillips III J, Posey J, Potocki L, Pusey B, Quinlan A, Raskind W, Raja A, Rao D, Renteria G, Reuter C, Rives L, Robertson A, Rodan L, Rosenfeld J, Rosenwasser N, Ruzhnikov M, Sacco R, Sampson J, Samson S, Saporta M, Scott C, Schaechter J, Schedl T, Schoch K, Scott D, Sharma P, Shashi V, Shin J, Signer R, Sillari C, Silverman E, Sinsheimer J, Sisco K, Smith E, Smith K, Solem E, Solnica-Krezel L, Spillmann R, Stoler J, StongJ N, Sullivan E, Sullivan K, Sun A, Sutton S, Sweetser D, Sybert V, Tabor H, Tamburro C, K-GTan Q, Tekin M, Telischi F, Thorson W, Tifft C, Toro C, Tran A, Tucker B, Urv T, Vanderver A, Velinder M, Viskochil D, Vogel T, Wahl C, Wallace S, Walley N, Walsh C, Walker M, Wambach J, Wan J, Wang L, Wangler M, Ward P, Wegner D, Wener M, Wenger T, Perry K, Westerfield M, Wheeler M, Whitlock J, Wolfe L, Woods J, Yamamoto S, Yang J, Yu G, Zastrow D, Zhao C, Zuchner S, Ariani F, Renieri A, Mari F, Wangler M, Arur S, Jiang Y, Yamamoto S, Shashi V, Bellen H. The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder. Human Molecular Genetics 2022, 31: 2934-2950. PMID: 35405010, PMCID: PMC9433733, DOI: 10.1093/hmg/ddac085.Peer-Reviewed Original ResearchConceptsWhite matter atrophyProgressive neurological disorderDe novo heterozygous variantsNovo heterozygous variantsProfound intellectual disabilityMatter atrophyNervous systemNeurological disordersHeterozygous variantsDysmorphic featuresMissense variantsSevere phenotypeIntellectual disabilityPhenotype characteristicLoss of DroshaLoss of miRNAMiRNA expressionBrain sizeSevere reductionSevere progressive neurological disorderFunctional studiesCauses lossAtrophyEpilepsyCandidate genes
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