Featured Publications
Modelling schizophrenia using human induced pluripotent stem cells
Brennand K, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage F. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473: 221-225. PMID: 21490598, PMCID: PMC3392969, DOI: 10.1038/nature09915.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntipsychotic AgentsCell DifferentiationCells, CulturedCellular ReprogrammingChildDisks Large Homolog 4 ProteinFemaleFibroblastsGene Expression ProfilingGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsLoxapineMaleMembrane ProteinsModels, BiologicalNeuritesNeuronsPhenotypePluripotent Stem CellsReceptors, GlutamateSchizophreniaYoung Adult
2021
Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor
Webb BD, Evans A, Naidich TP, Bird L, Parikh S, Garcia M, Henderson LB, Millan F, Si Y, Brennand KJ, Hung P, Rucker JC, Wheeler PG, Schadt EE. Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor. Human Mutation 2021, 42: 685-693. PMID: 33783914, PMCID: PMC8162891, DOI: 10.1002/humu.24201.Peer-Reviewed Original ResearchConceptsIntention tremorHead magnetic resonance imagingFunction variantsHypertrophic olivary degenerationCerebellar vermian atrophyMagnetic resonance imagingAtaxia syndromeWhole-exome sequencingVermian atrophyTranscription factor 1Olivary degenerationNervous systemResonance imagingMultiple abnormalitiesFactor 1POU4F1ProbandsSyndromeHypotoniaTremorClass 4De novoIndependent probandsAtrophyNewborns
2020
Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression
Issler O, van der Zee YY, Ramakrishnan A, Wang J, Tan C, Loh YE, Purushothaman I, Walker DM, Lorsch ZS, Hamilton PJ, Peña CJ, Flaherty E, Hartley BJ, Torres-Berrío A, Parise EM, Kronman H, Duffy JE, Estill MS, Calipari ES, Labonté B, Neve RL, Tamminga CA, Brennand KJ, Dong Y, Shen L, Nestler EJ. Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression. Neuron 2020, 106: 912-926.e5. PMID: 32304628, PMCID: PMC7305959, DOI: 10.1016/j.neuron.2020.03.023.Peer-Reviewed Original ResearchConceptsSex-specific phenotypesLong non-coding RNAsNon-coding RNAsStress resilienceHuman neuron-like cellsRegulatory transcriptsSex-specific patternsSex-specific roleNeuron-like cellsGene expressionFemale miceLong NonViral-mediated gene transferGene transferLINC00473Prefrontal cortexSynaptic functionRate of menPhenotypeCommon disorderPFC neuronsDepressed femalesDepressed humansFemale depressionComplex region
2019
Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development
Breen MS, Bierer LM, Daskalakis NP, Bader HN, Makotkine I, Chattopadhyay M, Xu C, Buxbaum Grice A, Tocheva AS, Flory JD, Buxbaum JD, Meaney MJ, Brennand K, Yehuda R. Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development. Translational Psychiatry 2019, 9: 201. PMID: 31434874, PMCID: PMC6704073, DOI: 10.1038/s41398-019-0539-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersConstitutive Androstane ReceptorDexamethasoneDose-Response Relationship, DrugGene ExpressionGene Expression ProfilingGene Regulatory NetworksGlucocorticoidsHumansLeukocytes, MononuclearMaleMiddle AgedStress Disorders, Post-TraumaticTranscription, GeneticVeteransYoung AdultConceptsPeripheral blood mononuclear cellsPost-traumatic stress disorderGlucocorticoid signalingCultured peripheral blood mononuclear cellsBlood immune cellsBlood mononuclear cellsTranscriptional responseConcentrations of dexamethasoneDifferential transcriptional changesGenome-wide gene expression profilingCombat-exposed veteransStress-responsive pathwaysMolecular responseClinical manifestationsInflammatory cytokinesDynamic transcriptional responseMononuclear cellsApoptosis-related pathwaysImmune cellsBaseline differencesDifferential transcriptional responsesDifferential molecular responsesGlucocorticoid stimulationNovel markerReliable marker
2017
Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Hoffman GE, Hartley BJ, Flaherty E, Ladran I, Gochman P, Ruderfer DM, Stahl EA, Rapoport J, Sklar P, Brennand KJ. Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains. Nature Communications 2017, 8: 2225. PMID: 29263384, PMCID: PMC5738408, DOI: 10.1038/s41467-017-02330-5.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, SurfaceAutopsyBrainCase-Control StudiesChildDNA Copy Number VariationsFemaleHumansInduced Pluripotent Stem CellsLinear ModelsMaleNanog Homeobox ProteinNestinNeural Stem CellsNeuronsOctamer Transcription Factor-3ProteoglycansRNA, MessengerSchizophreniaSequence Analysis, RNASOXB1 Transcription FactorsStage-Specific Embryonic AntigensSynapsinsTranscriptomeYoung AdultCommon developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS)
Narla S, Lee Y, Benson C, Sarder P, Brennand K, Stachowiak E, Stachowiak M. Common developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS). Schizophrenia Research 2017, 185: 17-32. PMID: 28094170, PMCID: PMC5507209, DOI: 10.1016/j.schres.2016.12.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell DifferentiationCells, CulturedFemaleGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenomeGenomicsHumansInduced Pluripotent Stem CellsMaleMicroRNAsModels, BiologicalMutationReceptor, Fibroblast Growth Factor, Type 1Receptor, Notch1SchizophreniaSignal TransductionTranscriptomeYoung AdultConceptsMRNA networkMajor developmental pathwaysIntegrative nuclear FGFR1MiRNA-mRNA networkHuman gene promotersCommon developmental genomesMiRNA genesMiRNA transcriptomeGene networksUpregulated genesGene promoterNuclear FGFR1Genomic etiologyGene dysregulationDisease ontogenyNuclear formGlobal dysregulationDevelopmental pathwaysGenesNeuron formationDistinct pathwaysConcerted actionPotential therapeutic targetTranscriptomeGenome
2015
Altered WNT Signaling in Human Induced Pluripotent Stem Cell Neural Progenitor Cells Derived from Four Schizophrenia Patients
Topol A, Zhu S, Tran N, Simone A, Fang G, Brennand K. Altered WNT Signaling in Human Induced Pluripotent Stem Cell Neural Progenitor Cells Derived from Four Schizophrenia Patients. Biological Psychiatry 2015, 78: e29-e34. PMID: 25708228, PMCID: PMC4520784, DOI: 10.1016/j.biopsych.2014.12.028.Peer-Reviewed Original Research
2014
Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia
Brennand K, Savas J, Kim Y, Tran N, Simone A, Hashimoto-Torii K, Beaumont K, Kim H, Topol A, Ladran I, Abdelrahim M, Matikainen-Ankney B, Chao S, Mrksich M, Rakic P, Fang G, Zhang B, Yates J, Gage F. Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Molecular Psychiatry 2014, 20: 361-368. PMID: 24686136, PMCID: PMC4182344, DOI: 10.1038/mp.2014.22.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntipsychotic AgentsCell DifferentiationCell MovementCells, CulturedFemaleGene ExpressionHumansMaleMiceMice, Inbred C57BLMice, TransgenicMitochondriaNeural Cell Adhesion MoleculesNeural Stem CellsOxidative StressPhenotypePluripotent Stem CellsProsencephalonProteomicsReactive Oxygen SpeciesSchizophreniaYoung AdultConceptsHiPSC neural progenitor cellsNeural progenitor cellsHuman-induced pluripotent stem cellsHiPSC-derived neuronsGene expressionGene expression comparisonsStable isotope labelingProteomic mass spectrometry analysisAbnormal gene expressionPluripotent stem cellsOxidative stressCytoskeletal remodelingMass spectrometry analysisCellular phenotypesExpression comparisonsDevelopmental mechanismsIsotope labelingPhenotypic differencesBrainSpan AtlasDisease predispositionAmino acidsScalable assayNPC phenotypeStem cellsProgenitor cells