Featured Publications
Neuronal impact of patient-specific aberrant NRXN1α splicing
Flaherty E, Zhu S, Barretto N, Cheng E, Deans PJM, Fernando MB, Schrode N, Francoeur N, Antoine A, Alganem K, Halpern M, Deikus G, Shah H, Fitzgerald M, Ladran I, Gochman P, Rapoport J, Tsankova NM, McCullumsmith R, Hoffman GE, Sebra R, Fang G, Brennand KJ. Neuronal impact of patient-specific aberrant NRXN1α splicing. Nature Genetics 2019, 51: 1679-1690. PMID: 31784728, PMCID: PMC7451045, DOI: 10.1038/s41588-019-0539-z.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAutism Spectrum DisorderBipolar DisorderCalcium-Binding ProteinsCase-Control StudiesDepressive Disorder, MajorFemaleGene ExpressionHeterozygoteHumansInduced Pluripotent Stem CellsMaleMiceNeural Cell Adhesion MoleculesProtein IsoformsSchizophreniaSequence DeletionModeling 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
2021
Analysis framework and experimental design for evaluating synergy-driving gene expression
Schrode N, Seah C, Deans P, Hoffman G, Brennand K. Analysis framework and experimental design for evaluating synergy-driving gene expression. Nature Protocols 2021, 16: 812-840. PMID: 33432232, PMCID: PMC8609447, DOI: 10.1038/s41596-020-00436-7.Peer-Reviewed Original ResearchConceptsRaw read countsPluripotent stem cell-derived neuronsRNA sequencing experimentsRNA sequencing datasetsStem cell-derived neuronsDifferential expression analysisCell-derived neuronsComplex genetic disorderNon-additive interactionsGenetic risk variantsChemical perturbagensBioinformatics skillsExpression analysisSequencing datasetsGene expressionTranscriptomic effectsSequencing experimentsComputational pipelineRead countsRisk variantsCareful experimental designCombinatorial manipulationGenetic variantsComplex diseasesPerturbation studies
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
Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease
Powell S, Gregory J, Akbarian S, Brennand K. Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease. Molecular And Cellular Neuroscience 2017, 82: 157-166. PMID: 28549865, PMCID: PMC5516945, DOI: 10.1016/j.mcn.2017.05.007.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBrainBrain DiseasesCRISPR-Cas SystemsGene EditingGene ExpressionHumansInduced Pluripotent Stem CellsConceptsCRISPR/Cas9 technologyPluripotent stem cellsTranscriptional regulatorsManipulation of DNAEpigenetic pathwaysGenomic editingSpecific lociCRISPR/Basic biologyCas9 technologyGene expressionStem cellsTargeted localizationEnzyme activityBrain developmentEpigenomeNeuropsychiatric diseasesGenomeCRISPRRepressionLociBiologyRegulatorEffectorsDNA
2015
Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells
Ho S, Hartley B, Julia T, Beaumont M, Stafford K, Slesinger P, Brennand K. Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods 2015, 101: 113-124. PMID: 26626326, PMCID: PMC4860098, DOI: 10.1016/j.ymeth.2015.11.019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsNeural progenitor cellsHiPSC-derived neural progenitor cellsHigh-throughput drug screeningHiPSC neural progenitor cellsExogenous transcription factorsProgenitor cellsInduced pluripotent stem cellsPatient-specific platformPluripotent stem cellsPatient-derived neuronsSomatic reprogrammingTranscription factorsGenetic variationExcitatory neuronsDrug screeningNeurogenin 2Neuronal inductionFunctional neuronsThroughput drug screeningNeuronal phenotypeLentiviral transductionStem cellsStarting populationDisease etiology
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 cellsModeling 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