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
2024
Single-cell multi-cohort dissection of the schizophrenia transcriptome
Ruzicka W, Mohammadi S, Fullard J, Davila-Velderrain J, Subburaju S, Tso D, Hourihan M, Jiang S, Lee H, Bendl J, Voloudakis G, Haroutunian V, Hoffman G, Roussos P, Kellis M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clarke D, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hwang A, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Sanders S, Schneider J, Scuderi S, Sebra R, Sestan N, Seyfried N, Shao Z, Shedd N, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Single-cell multi-cohort dissection of the schizophrenia transcriptome. Science 2024, 384: eadg5136. PMID: 38781388, DOI: 10.1126/science.adg5136.Peer-Reviewed Original ResearchConceptsGenetic risk factorsRisk factorsTranscriptional changesHeterogeneity of schizophreniaNeuronal cell statesSchizophrenia pathophysiologySingle-cell dissectionExcitatory neuronsEffective therapySchizophrenia transcriptomicsCortical cytoarchitectureSingle-cell atlasGenomic variantsCell groupsHuman prefrontal cortexMolecular pathwaysSchizophreniaTranscriptional alterationsTranscriptomic changesPrefrontal cortexCell statesAlterationsTherapyPathophysiologyDissectionMonozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission
Stern S, Zhang L, Wang M, Wright R, Rosh I, Hussein Y, Stern T, Choudhary A, Tripathi U, Reed P, Sadis H, Nayak R, Shemen A, Agarwal K, Cordeiro D, Peles D, Hang Y, Mendes A, Baul T, Roth J, Coorapati S, Boks M, McCombie W, Hulshoff Pol H, Brennand K, Réthelyi J, Kahn R, Marchetto M, Gage F. Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission. Molecular Psychiatry 2024, 29: 3208-3222. PMID: 38704507, PMCID: PMC11449799, DOI: 10.1038/s41380-024-02561-1.Peer-Reviewed Original ResearchCo-twinSchizophrenia patientsMonozygotic twinsHippocampal synaptic deficitsHealthy twinsSynapse-related genesDepressive disorderPsychiatric disordersSchizophreniaControl twinsTwin pairsSynaptic activitySynaptic deficitsTwin siblingsNeurophysiological abnormalitiesGroup of patientsSynaptic transmissionDiscordant twinsDisordersHippocampal neuronsNeuronsReprogrammed iPSCsIPSC modelsPatientsSiblings
2018
Expression-based drug screening of neural progenitor cells from individuals with schizophrenia
Readhead B, Hartley BJ, Eastwood BJ, Collier DA, Evans D, Farias R, He C, Hoffman G, Sklar P, Dudley JT, Schadt EE, Savić R, Brennand KJ. Expression-based drug screening of neural progenitor cells from individuals with schizophrenia. Nature Communications 2018, 9: 4412. PMID: 30356048, PMCID: PMC6200740, DOI: 10.1038/s41467-018-06515-4.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsHiPSC neural progenitor cellsCell typesCancer cell linesGene expression differencesProgenitor cellsDisease-associated genesPatient-specific platformPluripotent stem cellsTranscriptional responseExpression differencesTranscriptional signatureTranscriptomic signaturesStem cellsCell linesDependent mannerDrug discoveryDrug screeningCellsNeuropsychiatric disordersSchizophreniaBest treatmentDrugsDiscoveryGenes
2017
MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice
Mitchell A, Javidfar B, Pothula V, Ibi D, Shen E, Peter C, Bicks L, Fehr T, Jiang Y, Brennand K, Neve R, Gonzalez-Maeso J, Akbarian S. MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Molecular Psychiatry 2017, 23: 123-132. PMID: 28115742, PMCID: PMC5966823, DOI: 10.1038/mp.2016.254.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromatin ImmunoprecipitationCognition DisordersComputational BiologyDisease Models, AnimalEpigenomicsGene Expression RegulationGreen Fluorescent ProteinsHistonesMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsPolymorphism, Single NucleotideSchizophreniaTransduction, GeneticConceptsTherapeutic potentialPrefrontal projection neuronsNeuron-specific promoterUnexplored therapeutic potentialProjection neuronsDrug challengeDisease casesRelated disordersRisk architecturePrefrontal cortexSchizophreniaSingle nucleotide polymorphismsCognitive performancePsychiatric Genomics ConsortiumNeuronal genomeH3K4 hypermethylationRisk lociCognitive enhancement
2016
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells
Topol A, Zhu S, Hartley B, English J, Hauberg M, Tran N, Rittenhouse C, Simone A, Ruderfer D, Johnson J, Readhead B, Hadas Y, Gochman P, Wang Y, Shah H, Cagney G, Rapoport J, Gage F, Dudley J, Sklar P, Mattheisen M, Cotter D, Fang G, Brennand K. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells. Cell Reports 2016, 15: 1024-1036. PMID: 27117414, PMCID: PMC4856588, DOI: 10.1016/j.celrep.2016.03.090.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsControl neural progenitor cellsMiR-9 targetsProgenitor cellsSubset of patientsMiR-9Levels/activitiesMiR-9 expressionSchizophrenia patientsMicroRNA-9Migration deficitsDisease riskNeural migrationAberrant levelsAberrant migrationPatientsMiRNA-9SchizophreniaMigration-associated genesRNA sequencingSZ riskRiskIndirect targetsSubsetCells
2014
Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons
Hook V, Brennand K, Kim Y, Toneff T, Funkelstein L, Lee K, Ziegler M, Gage F. Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons. Stem Cell Reports 2014, 3: 531-538. PMID: 25358781, PMCID: PMC4223699, DOI: 10.1016/j.stemcr.2014.08.001.Peer-Reviewed Original ResearchConceptsHiPSC neuronsHuman-induced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsActivity-dependent secretionStem cell-derived neuronsCell-derived neuronsPositive neuronsCatecholamine levelsActivity-dependent mannerTyrosine hydroxylasePeptide neurotransmittersNeuronal culturesBrain disordersNeurotransmitter releaseChemical neurotransmissionKCl stimulationNeuronsNorepinephrineCatecholaminesElevated levelsNeurotransmitter secretionCatecholamine biosynthesisSchizophreniaDopamineNeurotransmitters
2013
Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells
Brennand K, Landek-Salgado M, Sawa A. Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells. Biological Psychiatry 2013, 75: 936-944. PMID: 24331955, PMCID: PMC4022707, DOI: 10.1016/j.biopsych.2013.10.025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCommon clinical manifestationsSmall patient cohortPathology of schizophreniaStem cellsPluripotent stem cellsComplex genetic conditionClinical manifestationsPatient cohortClinical etiologyHuman neuronsAnimal modelsClinical heterogeneityHeterogeneous patientsClinical diagnosisSchizophreniaGenetic conditionsMental conditionPatientsGenetic variantsBiological mechanismsClinical constraintsRare genetic variantsCellsCohortEtiology
2012
Modeling Schizophrenia Using Induced Pluripotent Stem Cell–Derived and Fibroblast-Induced Neurons
Tran N, Ladran I, Brennand K. Modeling Schizophrenia Using Induced Pluripotent Stem Cell–Derived and Fibroblast-Induced Neurons. Schizophrenia Bulletin 2012, 39: 4-10. PMID: 23172000, PMCID: PMC3523925, DOI: 10.1093/schbul/sbs127.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsModeling psychiatric disorders at the cellular and network levels
Brennand K, Simone A, Tran N, Gage F. Modeling psychiatric disorders at the cellular and network levels. Molecular Psychiatry 2012, 17: 1239-1253. PMID: 22472874, PMCID: PMC3465628, DOI: 10.1038/mp.2012.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCell-based studiesPluripotent stem cell-derived neuronsStem cell-derived neuronsLive human neuronsCell-derived neuronsPsychiatric disordersBasic phenotypesGenetic backgroundHuman neuronsClinical symptomsComplex arrayBipolar disorderBrain regionsDisease statesNeuronsSingle neuronsDisordersLimitless numberAutism spectrum disorderSpectrum disorderPhenotypeFibroblastsPatientsSymptomsSchizophrenia