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
2020
Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanisms
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 proliferationTHC 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
2016
Activity-Dependent Changes in Gene Expression in Schizophrenia Human-Induced Pluripotent Stem Cell Neurons
Roussos P, Guennewig B, Kaczorowski D, Barry G, Brennand K. Activity-Dependent Changes in Gene Expression in Schizophrenia Human-Induced Pluripotent Stem Cell Neurons. JAMA Psychiatry 2016, 73: 1180-1188. PMID: 27732689, PMCID: PMC5437975, DOI: 10.1001/jamapsychiatry.2016.2575.Peer-Reviewed Original ResearchConceptsGene coexpression analysisActivity-dependent changesGene expressionCandidate genesCoexpression analysisSchizophrenia candidate genesSpecific molecular functionsGenome-wide profilingPluripotent stem cell-derived neuronsGene expression differencesSchizophrenia-associated variantsStem cell-derived neuronsDifferential expression analysisNeuronal activity-dependent changesHuman-induced pluripotent stem cell-derived neuronsCell-derived neuronsHuman-induced pluripotent stem cellsPluripotent stem cell neuronsPluripotent stem cellsCommon molecular pathwaysSchizophrenia risk genesMolecular functionsGene networksEtiopathogenesis of schizophreniaExpression analysis
2014
A Role for Noncoding Variation in Schizophrenia
Roussos P, Mitchell A, Voloudakis G, Fullard J, Pothula V, Tsang J, Stahl E, Georgakopoulos A, Ruderfer D, Charney A, Okada Y, Siminovitch K, Worthington J, Padyukov L, Klareskog L, Gregersen P, Plenge R, Raychaudhuri S, Fromer M, Purcell S, Brennand K, Robakis N, Schadt E, Akbarian S, Sklar P. A Role for Noncoding Variation in Schizophrenia. Cell Reports 2014, 9: 1417-1429. PMID: 25453756, PMCID: PMC4255904, DOI: 10.1016/j.celrep.2014.10.015.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCalcium Channels, L-TypeDatabases, GeneticDNA, IntergenicEnhancer Elements, GeneticGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMolecular Sequence AnnotationOrgan SpecificityPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingRisk FactorsSchizophreniaConceptsExpression quantitative trait lociGenome-wide significant lociCommon variant lociQuantitative trait lociPluripotent stem cell-derived neuronsDistal regulatory elementsStem cell-derived neuronsPotential physical interactionsCell-derived neuronsRegulatory element sequencesPotential functional roleGenome architectureChromosomal loopingTranscriptional regulationFunctional annotationTrait lociSignificant lociNoncoding SNPsRegulatory elementsNoncoding variationsRisk lociVariant lociUnknown functionFunctional linkElement sequencesHuman 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
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
Investigating synapse formation and function using human pluripotent stem cell-derived neurons
Kim J, O'Sullivan M, Sanchez C, Hwang M, Israel M, Brennand K, Deerinck T, Goldstein L, Gage F, Ellisman M, Ghosh A. Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 3005-3010. PMID: 21278334, PMCID: PMC3041068, DOI: 10.1073/pnas.1007753108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Adhesion Molecules, NeuronalCell DifferentiationChild Development Disorders, PervasiveDNA PrimersElectrophysiologyEmbryonic Stem CellsFluorescent Antibody TechniqueHEK293 CellsHumansInfant, NewbornMembrane ProteinsMicroscopy, ElectronMutationNerve Tissue ProteinsNeuronsPluripotent Stem CellsProsencephalonRatsReverse Transcriptase Polymerase Chain ReactionSynapsesTransfectionConceptsPluripotent stem cell-derived neuronsStem cell-derived neuronsCell-derived neuronsHuman pluripotent stem cell-derived neuronsStem cellsHuman embryonic stem cellsSynapse formationEmbryonic stem cellsSpecific cell typesHEK293T cellsPluripotent stem cellsHuman stem cellsAutism-associated mutationPresynaptic differentiationFrame deletionStem cell researchCell typesCell surfaceSynaptic differentiationVivo transplantationDifferentiationNLGN4Neuroligin-3CellsDrug development