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 Deletion
2024
Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariants
2017
Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Hoffman GE, Hartley BJ, Flaherty E, Ladran I, Gochman P, Ruderfer DM, Stahl EA, Rapoport J, Sklar P, Brennand KJ. Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains. Nature Communications 2017, 8: 2225. PMID: 29263384, PMCID: PMC5738408, DOI: 10.1038/s41467-017-02330-5.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, SurfaceAutopsyBrainCase-Control StudiesChildDNA Copy Number VariationsFemaleHumansInduced Pluripotent Stem CellsLinear ModelsMaleNanog Homeobox ProteinNestinNeural Stem CellsNeuronsOctamer Transcription Factor-3ProteoglycansRNA, MessengerSchizophreniaSequence Analysis, RNASOXB1 Transcription FactorsStage-Specific Embryonic AntigensSynapsinsTranscriptomeYoung Adult
2016
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells
Topol A, Zhu S, Hartley B, English J, Hauberg M, Tran N, Rittenhouse C, Simone A, Ruderfer D, Johnson J, Readhead B, Hadas Y, Gochman P, Wang Y, Shah H, Cagney G, Rapoport J, Gage F, Dudley J, Sklar P, Mattheisen M, Cotter D, Fang G, Brennand K. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells. Cell Reports 2016, 15: 1024-1036. PMID: 27117414, PMCID: PMC4856588, DOI: 10.1016/j.celrep.2016.03.090.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsControl neural progenitor cellsMiR-9 targetsProgenitor cellsSubset of patientsMiR-9Levels/activitiesMiR-9 expressionSchizophrenia patientsMicroRNA-9Migration deficitsDisease riskNeural migrationAberrant levelsAberrant migrationPatientsMiRNA-9SchizophreniaMigration-associated genesRNA sequencingSZ riskRiskIndirect targetsSubsetCells
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 biosynthesisSchizophreniaDopamineNeurotransmitters