Featured Publications
Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression
Seah C, Breen M, Rusielewicz T, Bader H, Xu C, Hunter C, McCarthy B, Deans P, Chattopadhyay M, Goldberg J, Desarnaud F, Makotkine I, Flory J, Bierer L, Staniskyte M, Noggle S, Huckins L, Paull D, Brennand K, Yehuda R. Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression. Nature Neuroscience 2022, 25: 1434-1445. PMID: 36266471, PMCID: PMC9630117, DOI: 10.1038/s41593-022-01161-y.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderPeripheral blood mononuclear cellsGlucocorticoid-induced changesGlucocorticoid-induced gene expressionBlood mononuclear cellsIndividual clinical outcomesEnvironmental risk factorsHuman postmortem brainGlucocorticoid hypersensitivityClinical outcomesGlutamatergic neuronsMononuclear cellsRisk factorsHydrocortisone exposureSevere traumaPostmortem brainsHuman neuronsGlucocorticoid responseInduced neuronsStress disorderNeuronsNew therapeuticsGene expressionGene × environment interactionsCombat veteransModelling 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
Monozygotic 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, 1-15. PMID: 38704507, 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
2023
Modeling Gene by Environment Interactions in Post-Traumatic Stress Disorder Across the Post-Mortem Brain and in hiPSC-Derived Neurons
Seah C, Signer R, Young H, Rusielewicz T, Bader H, Xu C, dePins A, Breen M, Paull D, Girgenti M, Yehuda R, Brennand K, Huckins L. Modeling Gene by Environment Interactions in Post-Traumatic Stress Disorder Across the Post-Mortem Brain and in hiPSC-Derived Neurons. Biological Psychiatry 2023, 93: s11. DOI: 10.1016/j.biopsych.2023.02.048.Peer-Reviewed Original Research
2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populationsUsing the dCas9-KRAB system to repress gene expression in hiPSC-derived NGN2 neurons
Li A, Cartwright S, Yu A, Ho SM, Schrode N, Deans PJM, Matos MR, Garcia MF, Townsley KG, Zhang B, Brennand KJ. Using the dCas9-KRAB system to repress gene expression in hiPSC-derived NGN2 neurons. STAR Protocols 2021, 2: 100580. PMID: 34151300, PMCID: PMC8188621, DOI: 10.1016/j.xpro.2021.100580.Peer-Reviewed Original ResearchConceptsCRISPR inhibitionGene expressionDCas9-KRAB systemEndogenous gene expressionMultiple target genesGene repressionGene activationTarget genesGene manipulationFusion proteinComplete detailsPluripotent stemExpressionGlutamatergic neuronsRepressionGenesPhenotypicProteinStemNeuronsActivationBrain diseasesInhibitionCircadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies
Mishra H, Ying N, Luis A, Wei H, Nguyen M, Nakhla T, Vandenburgh S, Alda M, Berrettini W, Brennand K, Calabrese J, Coryell W, Frye M, Gage F, Gershon E, McInnis M, Nievergelt C, Nurnberger J, Shilling P, Oedegaard K, Zandi P, Kelsoe J, Welsh D, McCarthy M. Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies. Molecular Psychiatry 2021, 26: 3383-3394. PMID: 33674753, PMCID: PMC8418615, DOI: 10.1038/s41380-021-01048-7.Peer-Reviewed Original ResearchConceptsNeuronal precursor cellsBipolar disorderCircadian rhythm abnormalitiesRhythm abnormalitiesBD groupCircadian rhythmPatient-derived neuronsMania/hypomaniaExpression of Per2Induced pluripotent stem cellsPER2 protein levelsGlutamatergic neuronsRecurrent episodesBD patientsControl neuronsLithium respondersEffective drugsNeuropsychiatric illnessLithium responsivenessPatient neuronsNeuronsLithium responseProtein levelsRhythm deficitsPrecursor cellsXenopus models suggest convergence of gene signatures on neurogenesis in autism
Brennand K, Talkowski M. Xenopus models suggest convergence of gene signatures on neurogenesis in autism. Neuron 2021, 109: 743-745. PMID: 33662268, DOI: 10.1016/j.neuron.2021.02.017.Commentaries, Editorials and Letters
2020
Differential Transcriptional Responses to Glucocorticoid Activation in Cultured Blood Immune Cells and Neurons: A Novel Approach to PTSD Biomarker Development
Breen M, Bierer L, Bader H, Makotkine I, Flory J, Meaney M, Brennand K, Yehuda R. Differential Transcriptional Responses to Glucocorticoid Activation in Cultured Blood Immune Cells and Neurons: A Novel Approach to PTSD Biomarker Development. Biological Psychiatry 2020, 87: s49-s50. DOI: 10.1016/j.biopsych.2020.02.151.Peer-Reviewed Original ResearchTranscriptional Signatures of Participant-Derived Neural Progenitor Cells and Neurons Implicate Altered WNT Signaling in Phelan-McDermid Syndrome and Autism
Breen M, Browne A, Hoffman G, Stathopoulous S, Brennand K, Buxbaum J, Drapeau E. Transcriptional Signatures of Participant-Derived Neural Progenitor Cells and Neurons Implicate Altered WNT Signaling in Phelan-McDermid Syndrome and Autism. Biological Psychiatry 2020, 87: s456-s457. DOI: 10.1016/j.biopsych.2020.02.1162.Peer-Reviewed Original Research
2018
THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders
Guennewig B, Bitar M, Obiorah I, Hanks J, O’Brien E, Kaczorowski DC, Hurd YL, Roussos P, Brennand KJ, Barry G. THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Translational Psychiatry 2018, 8: 89. PMID: 29691375, PMCID: PMC5915454, DOI: 10.1038/s41398-018-0137-3.Peer-Reviewed Original ResearchConceptsHuman-induced pluripotent stem cellsPluripotent stem cellsHuman iPSC neuronsTranscriptional responseTranscriptomic analysisRNA transcriptomic analysisHuman neural cellsIPSC-neuronsMolecular pathwaysNeuropsychiatric disordersStem cellsNeural cellsDiagnosis-specific differencesGenesTHC exposureNeuronal depolarizationTHC administrationChronic exposureCannabis useNeuronsΔ9-tetrahydrocannabinolStrong associationSignificant alterationsCellsDynamic changesModeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons
Chandrasekaran S, Rajarajan P, Akbarian S, Brennand K. Modeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons. 2018, 119-157. DOI: 10.1002/9781119283249.ch6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHuman induced pluripotent stem cellsInduced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsStem cell-derived neuronsZika virus epidemicPathophysiological mechanismsNeurological diseasesInduction protocolNeuropsychiatric diseasesCerebral organoidsTranslational benefitsVirus epidemicDrug testingDisease treatmentInduced pluripotent stem cellsDiseaseNeuronsStem cellsOptimization of differentiationPluripotent stem cellsSpecific subsetNeuroscience researchCulture dishesTransplantationBrain
2017
Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human Induced Pluripotent Stem Cells
Prytkova I, Brennand K. Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human Induced Pluripotent Stem Cells. Frontiers In Cellular Neuroscience 2017, 11: 360. PMID: 29217999, PMCID: PMC5703699, DOI: 10.3389/fncel.2017.00360.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInhibitory GABAergic neuronsAbnormal neuronal functionStem cellsPluripotent stem cellsGABAergic neuronsDopaminergic neuronsNetwork dysfunctionSZ pathologyDifficult disorderPatient-derived pluripotent stem cellsGlial culturesAnimal modelsNeuronal functionNetwork pathologyPatient-specific mannerHuman induced pluripotent stem cellsMolecular dysfunctionCo-culture techniqueInduced pluripotent stem cellsDysfunctionHigh rateDifferent cell typesNeuronsPathologyCell typesTHC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons
Obiorah I, Muhammad H, Stafford K, Flaherty E, Brennand K. THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons. Complex Psychiatry 2017, 3: 73-84. PMID: 29230395, PMCID: PMC5701275, DOI: 10.1159/000477762.Peer-Reviewed Original ResearchTHC exposureHuman-induced pluripotent stem cellsGlutamate receptor gene expressionHuman stem cell-derived neuronsHiPSC-derived neuronsStem cell-derived neuronsΔ9-tetrahydrocannabinol exposureGlutamate receptor subunit genesCell-derived neuronsGenetic risk factorsReceptor gene expressionRisk factorsExcitatory neuronsHuman neuronsReceptor subunit genesBehavioral effectsNeuronsDisease vulnerabilityStem cellsPluripotent stem cellsExposureVariety of genotypesGene expressionExpressionSubunit gene
2015
A new recipe for serotonergic neurons
Brennand K. A new recipe for serotonergic neurons. Science Translational Medicine 2015, 7 DOI: 10.1126/scitranslmed.aad5908.Commentaries, Editorials and LettersDifferential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
Mertens J, Wang Q, Kim Y, Yu D, Pham S, Yang B, Zheng Y, Diffenderfer K, Zhang J, Soltani S, Eames T, Schafer S, Boyer L, Marchetto M, Nurnberger J, Calabrese J, Oedegaard K, McCarthy M, Zandi P, Alda M, Nievergelt C, Mi S, Brennand K, Kelsoe J, Gage F, Yao J. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 2015, 527: 95-99. PMID: 26524527, PMCID: PMC4742055, DOI: 10.1038/nature15526.Peer-Reviewed Original ResearchCharacterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells
Lee I, Carvalho C, Douvaras P, Ho S, Hartley B, Zuccherato L, Ladran I, Siegel A, McCarthy S, Malhotra D, Sebat J, Rapoport J, Fossati V, Lupski J, Levy D, Brennand K. Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells. Schizophrenia 2015, 1: 15019. PMID: 26985448, PMCID: PMC4789165, DOI: 10.1038/npjschz.2015.19.Peer-Reviewed Original ResearchClinical outcomesCNTNAP2 expressionHiPSC neural progenitor cellsDiscordant clinical outcomesHiPSC-derived neuronsOligodendrocyte precursor cellsNeural progenitor cellsContactin-associated proteinHuman neuronsAnimal modelsClinical settingGenetic deletionExpression patternsNeural cellsProgenitor cellsLarge heterozygous deletionsNeurodevelopmental disordersPrecursor cellsDisordersComplex disorderHeterozygous deletionSignificant differencesNeuronsStem cellsExon 14From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease
Ho S, Topol A, Brennand K. From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease. Biomarker Insights 2015, 10s1: bmi.s20066. PMID: 26045654, PMCID: PMC4444490, DOI: 10.4137/bmi.s20066.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeuronal inductionSomatic cell reprogrammingNeuropsychiatric diseasesPsychiatric disordersPluripotent stem cell (iPSC) technologyCell reprogrammingDirected DifferentiationMost neurological diseasesStem cell technologyHuman postmortem samplesFunction of neuronsPolygenic originHuman neuronsDisease onsetAnimal modelsNeurological diseasesDisease initiationPostmortem samplesDiseaseNeuronsDifferentiationPrimary causeLimitless numberDisordersAberrant behavior
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 biosynthesisSchizophreniaDopamineNeurotransmittersModeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells
Yu D, Di Giorgio F, Yao J, Marchetto M, Brennand K, Wright R, Mei A, Mchenry L, Lisuk D, Grasmick J, Silberman P, Silberman G, Jappelli R, Gage F. Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells. Stem Cell Reports 2014, 2: 295-310. PMID: 24672753, PMCID: PMC3964286, DOI: 10.1016/j.stemcr.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsCell DifferentiationDentate GyrusElectrophysiological PhenomenaEmbryoid BodiesGene ExpressionGenes, ReporterHippocampusHomeodomain ProteinsHumansNerve NetNeural Stem CellsNeurogenesisNeuronsNeurotransmitter AgentsPluripotent Stem CellsPyramidal CellsSchizophreniaTumor Suppressor ProteinsConceptsHippocampal neurogenesisDentate gyrusHippocampal dentate gyrusDG granule neuronsStem cellsPluripotent stem cellsSpontaneous neurotransmitter releaseNeuronal network maturationPatient-derived humanHuman pluripotent stem cellsDifferentiation paradigmNeuronal activityGranule neuronsBrain regionsNeurotransmitter releaseNeurodevelopmental aspectsLineage-specific cellsNeurogenesisNeuronsNetwork maturationReduced levelsPersonalized medicineHuman diseasesCellsDrug screening