Featured Publications
Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk
Rajarajan P, Borrman T, Liao W, Schrode N, Flaherty E, Casiño C, Powell S, Yashaswini C, LaMarca EA, Kassim B, Javidfar B, Espeso-Gil S, Li A, Won H, Geschwind DH, Ho SM, MacDonald M, Hoffman GE, Roussos P, Zhang B, Hahn CG, Weng Z, Brennand KJ, Akbarian S. Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk. Science 2018, 362 PMID: 30545851, PMCID: PMC6408958, DOI: 10.1126/science.aat4311.Peer-Reviewed Original ResearchMeSH KeywordsBrainCells, CulturedChromatinChromatin Assembly and DisassemblyChromosomes, HumanConnectomeEpigenesis, GeneticGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansMaleNeural Stem CellsNeurogenesisNeurogliaNeuronsNucleic Acid ConformationProtein Interaction MapsProteomicsRiskSchizophreniaTranscription, GeneticTranscriptomeConceptsCoordinated transcriptional regulationThree-dimensional genomeSpatial genome organizationChromosomal contact mapsNeural progenitor cellsSchizophrenia risk variantsGenome organizationChromatin remodelingChromosomal conformationTranscriptional regulationProteomic interactionsDevelopmental remodelingHeritable riskGlial differentiationRisk variantsContact mapsProgenitor cellsVariant sequencesGenesConformation changeNeuronal connectivitySchizophrenia riskSequenceNeuropsychiatric diseasesDistal targets
2023
Multi-omic profiling of the developing human cerebral cortex at the single-cell level
Zhu K, Bendl J, Rahman S, Vicari J, Coleman C, Clarence T, Latouche O, Tsankova N, Li A, Brennand K, Lee D, Yuan G, Fullard J, Roussos P. Multi-omic profiling of the developing human cerebral cortex at the single-cell level. Science Advances 2023, 9: eadg3754. PMID: 37824614, PMCID: PMC10569714, DOI: 10.1126/sciadv.adg3754.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsChromatin accessibilityGene expressionPseudotime trajectory analysisNeuronal lineage commitmentMulti-omics profilingSingle-cell levelSpecific genetic lociDevelopmental time pointsChromatin structureType-specific domainsLineage determinationCellular complexityLineage commitmentNeuropsychiatric traitsComplex regulationGenetic lociSpatiotemporal activityDynamic changesCritical roleExpressionSpatiotemporal alterationsCell compositionCritical stageNeuropsychiatric diseases
2022
Population-level variation in enhancer expression identifies disease mechanisms in the human brain
Dong P, Hoffman G, Apontes P, Bendl J, Rahman S, Fernando M, Zeng B, Vicari J, Zhang W, Girdhar K, Townsley K, Misir R, Brennand K, Haroutunian V, Voloudakis G, Fullard J, Roussos P. Population-level variation in enhancer expression identifies disease mechanisms in the human brain. Nature Genetics 2022, 54: 1493-1503. PMID: 36163279, PMCID: PMC9547946, DOI: 10.1038/s41588-022-01170-4.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociPopulation-level variationTranscriptome-wide association studyQuantitative trait lociSpecific transcriptomeTrait lociTrait heritabilitySpecific transcriptionEnhancer functionGenetic mechanismsTarget genesAssociation studiesDisease locusNeuropsychiatric diseasesRisk variantsGenesRobust expressionTranscriptomeFunctional interpretationDisease mechanismsEnhancerDiseased statesLociHuman brainBrain samples
2019
CRISPR-based functional evaluation of schizophrenia risk variants
Rajarajan P, Flaherty E, Akbarian S, Brennand KJ. CRISPR-based functional evaluation of schizophrenia risk variants. Schizophrenia Research 2019, 217: 26-36. PMID: 31277978, PMCID: PMC6939156, DOI: 10.1016/j.schres.2019.06.017.Peer-Reviewed Original ResearchConceptsSchizophrenia-associated variantsPluripotent stem cellsCRISPR genome engineeringSchizophrenia risk variantsCellular functionsGenome engineeringGenomic studiesSchizophrenia lociList of variantsGene expressionPatient-specific humanGenotype dataRisk variantsStem cellsFunctional impactCommon variantsCRISPRPost-mortem brain tissueRecent findingsVariantsNeuropsychiatric diseasesPoint of convergenceGenetic riskLociSpecific effects
2018
Modeling 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
Personalized medicine in a dish: the growing possibility of neuropsychiatric disease drug discovery tailored to patient genetic variants using stem cells
Brennand K. Personalized medicine in a dish: the growing possibility of neuropsychiatric disease drug discovery tailored to patient genetic variants using stem cells. Stem Cell Investigation 2017, 4: 91-91. PMID: 29270417, PMCID: PMC5723749, DOI: 10.21037/sci.2017.10.05.Commentaries, Editorials and LettersNeural progenitor cellsBrain disordersNeural cell fateNeuropsychiatric diseasesStem cellsZika virus infectionPatient genetic variantsCell-derived neuronsPluripotent stem cellsHuman neural cellsCell fateDisease drug discoveryDisease progressionHealthy controlsNeural differentiationVirus infectionMature neuronsParkinson's diseasePhenotypic changesCellular insightsPatient's genotypeZika virusAlzheimer's diseaseBrain tissueNeural proliferationApplication 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 StatementsConceptsCRISPR/Cas9 technologyPluripotent stem cellsTranscriptional regulatorsManipulation of DNAEpigenetic pathwaysGenomic editingSpecific lociCRISPR/Basic biologyCas9 technologyGene expressionStem cellsTargeted localizationEnzyme activityBrain developmentEpigenomeNeuropsychiatric diseasesGenomeCRISPRRepressionLociBiologyRegulatorEffectorsDNA
2015
From “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