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 veterans
2023
Convergent coexpression of autism-associated genes suggests some novel risk genes may not be detectable in large-scale genetic studies
Liao C, Moyses-Oliveira M, De Esch C, Bhavsar R, Nuttle X, Li A, Yu A, Burt N, Erdin S, Fu J, Wang M, Morley T, Han L, Consortium C, Dion P, Rouleau G, Zhang B, Brennand K, Talkowski M, Ruderfer D. Convergent coexpression of autism-associated genes suggests some novel risk genes may not be detectable in large-scale genetic studies. Cell Genomics 2023, 3: 100277. PMID: 37082147, PMCID: PMC10112287, DOI: 10.1016/j.xgen.2023.100277.Peer-Reviewed Original ResearchRisk genesNovel risk genesProtein-altering variantsLarge-scale genetic studiesASD risk genesHeritable neurodevelopmental disorderAutism-associated genesCRISPR perturbationsConvergent genesNovel genesTranscriptional consequencesFunctional mutationsGenetic studiesCoexpression patternsDifferential expressionGenesHuman neuronsASD-associationHuman postmortem brainRare variationCoexpressionASD brainNeurodevelopmental disordersPostmortem brainsMutations
2022
Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
Farrelly L, Zheng S, Schrode N, Topol A, Bhanu N, Bastle R, Ramakrishnan A, Chan J, Cetin B, Flaherty E, Shen L, Gleason K, Tamminga C, Garcia B, Li H, Brennand K, Maze I. Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia. Nature Communications 2022, 13: 2195. PMID: 35459277, PMCID: PMC9033776, DOI: 10.1038/s41467-022-29922-0.Peer-Reviewed Original ResearchConceptsHistone posttranslational modificationsPosttranslational modificationsUnbiased proteomic approachPluripotent stem cellsPatient-derived neuronsH2A.Z acetylationChromatin profilingHyperacetylated histonesFamily proteinsProteomic approachProtein interactionsHistone acetylationTranscriptional abnormalitiesEpigenetic factorsExtraterminal (BET) proteinsSZ casesRisk variantsHuman neuronsStem cellsAberrant roleProtein inhibitionBona fideTreatment of schizophreniaPostmortem human brainCritical role
2021
Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes
Ikegame S, Hashiguchi T, Hung C, Dobrindt K, Brennand K, Takeda M, Lee B. Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2026027118. PMID: 33903248, PMCID: PMC8106313, DOI: 10.1073/pnas.2026027118.Peer-Reviewed Original ResearchConceptsF mutantsMeasles inclusion body encephalitisBSR-T7 cellsMeasles virus F proteinReceptor-binding proteinVirus F proteinGenomic contextFitness advantageWild-type MeVRegulatory domainHyperfusogenic phenotypePrimary human neuronsMutant libraryPoint mutantsMutantsFitness selectionMeV receptorsF phenotypeInclusion body encephalitisNeuropathogenic phenotypeFitness landscapeChronic latent infectionFusion geneF proteinHuman neurons
2020
Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems
Rehbach K, Fernando MB, Brennand KJ. Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems. Journal Of Neuroscience 2020, 40: 1176-1185. PMID: 32024766, PMCID: PMC7002154, DOI: 10.1523/jneurosci.0518-19.2019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsMajor brain cell typesDual Perspectives CompanionBrain cell typesNeuronal maturityPsychiatric disordersHuman neuronsDisease riskStudy designBrain organoidsIntradonor variabilityDisease modelsHuman neurodevelopmentInduced pluripotent stem cellsNeural differentiationDiseaseStem cellsCell typesPluripotent stem cellsHuman diseasesEfficient neural differentiationInduction strategyPatient-specific cellsDisease modelingCells
2017
THC 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
Characterization 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
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 variantsCellsCohortEtiologyMosaic Copy Number Variation in Human Neurons
McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T, Cowing-Zitron C, Shumilina S, Lasken RS, Vermeesch JR, Hall IM, Gage FH. Mosaic Copy Number Variation in Human Neurons. Science 2013, 342: 632-637. PMID: 24179226, PMCID: PMC3975283, DOI: 10.1126/science.1243472.Peer-Reviewed Original ResearchConceptsCopy number variationsHiPSC-derived neuronsSingle-cell genomic approachesNumber variationsDNA copy number variationsSingle-cell sequencingHuman neuronsLarge copy number variationsStem cell linesNeural progenitor cellsNovo copy-number variationsPluripotent stem cell lineAneuploid neuronsGenomic approachesDe novo copy-number variationsSubchromosomal copy number variationsAberrant genomesFrontal cortex neuronsLarge deletionsProgenitor cellsCell linesSubset of neuronsEuploid neuronsDeletionMultiple alterations
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
2011
Concise Review: The Promise of Human Induced Pluripotent Stem Cell‐Based Studies of Schizophrenia
Brennand K, Gage F. Concise Review: The Promise of Human Induced Pluripotent Stem Cell‐Based Studies of Schizophrenia. Stem Cells 2011, 29: 1915-1922. PMID: 22009633, PMCID: PMC3381343, DOI: 10.1002/stem.762.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGenome-wide association studiesHuman induced pluripotent stem cellsHiPSC neuronsMolecular mechanismsStem cell-based studiesGene expression changesLive human neuronsInduced pluripotent stem cellsPluripotent stem cellsCommon single nucleotide polymorphismsRare copy number variantsCell-based studiesCopy number variantsSingle nucleotide polymorphismsExpression changesAssociation studiesCellular defectsHuman diseasesPost-mortem humanHeritable developmental disorderNumber variantsNucleotide polymorphismsHuman neuronsStem cellsGenesModeling psychiatric disorders through reprogramming
Brennand K, Gage F. Modeling psychiatric disorders through reprogramming. Disease Models & Mechanisms 2011, 5: 26-32. PMID: 21954066, PMCID: PMC3255540, DOI: 10.1242/dmm.008268.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements