Featured Publications
Modelling schizophrenia using human induced pluripotent stem cells
Brennand K, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage F. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473: 221-225. PMID: 21490598, PMCID: PMC3392969, DOI: 10.1038/nature09915.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntipsychotic AgentsCell DifferentiationCells, CulturedCellular ReprogrammingChildDisks Large Homolog 4 ProteinFemaleFibroblastsGene Expression ProfilingGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsLoxapineMaleMembrane ProteinsModels, BiologicalNeuritesNeuronsPhenotypePluripotent Stem CellsReceptors, GlutamateSchizophreniaYoung Adult
2021
Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection
Dobrindt K, Hoagland DA, Seah C, Kassim B, O'Shea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Møller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports 2021, 16: 505-518. PMID: 33636110, PMCID: PMC7881728, DOI: 10.1016/j.stemcr.2021.02.010.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCOVID-19FemaleFurinGenetic Predisposition to DiseaseHost-Pathogen InteractionsHumansInduced Pluripotent Stem CellsMaleNeuronsPeptide HydrolasesPolymorphism, Single NucleotideSARS-CoV-2Vero CellsConceptsSARS-CoV-2Clinical complicationsSARS-CoV-2 infectionCommon genetic variationHigh-risk individualsHost genetic variantsSignificant interindividual variabilityNeuron infectionUnderlying comorbiditiesViral loadHealthy individualsViral infectionClinical heterogeneityVitro SusceptibilityEtiologic agentHost responseInterindividual variabilityDiscovery of drugsInfectionHost geneticsHuman induced pluripotent stem cellsSingle nucleotide polymorphismsAntibody repertoireMore diseasesComplications
2020
Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism
Breen MS, Browne A, Hoffman GE, Stathopoulos S, Brennand K, Buxbaum JD, Drapeau E. Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism. Molecular Autism 2020, 11: 53. PMID: 32560742, PMCID: PMC7304190, DOI: 10.1186/s13229-020-00355-0.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutistic DisorderChildChild, PreschoolChromosome DeletionChromosome DisordersChromosomes, Human, Pair 22FemaleGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsMaleNeural Stem CellsNeuronsReproducibility of ResultsWnt Signaling PathwayConceptsNeural progenitor cellsTranscriptional signatureGene co-expression network analysisHiPSC-NPCsCo-expression network analysisIndependent biological samplesHiPSC-derived neural cellsProgenitor cellsPostsynaptic density genesDistinct transcriptional signaturesGenetic risk lociHuman-induced pluripotent stem cellsPluripotent stem cellsPotassium channel activityProtein translationSpecific neurobiological pathwaysTranscriptional differencesEmbryonic developmentLoss of SHANK3Risk lociHiPSC neuronsMorphological phenotypesWnt pathwayGenesHiPSC clones
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 AdultHigh-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain
Zhou T, Tan L, Cederquist G, Fan Y, Hartley B, Mukherjee S, Tomishima M, Brennand K, Zhang Q, Schwartz R, Evans T, Studer L, Chen S. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Cell Stem Cell 2017, 21: 274-283.e5. PMID: 28736217, PMCID: PMC5553280, DOI: 10.1016/j.stem.2017.06.017.Peer-Reviewed Original ResearchConceptsZIKV infectionNeurological complicationsZika virusZIKV-infected patientsSerious neurological complicationsZika virus infectionCortical neural progenitor cellsForebrain organoidsAdult mouse brainHigh-content chemical screenDrug candidatesNeural progenitor cellsAdult patientsHuman forebrain organoidsVirus infectionMouse modelAdult brainAdult miceMouse brainTherapeutic potentialTherapeutic treatmentInfectionProgenitor cellsBrainComplications
2016
Altered proliferation and networks in neural cells derived from idiopathic autistic individuals
Marchetto M, Belinson H, Tian Y, Freitas B, Fu C, Vadodaria K, Beltrao-Braga P, Trujillo C, Mendes A, Padmanabhan K, Nunez Y, Ou J, Ghosh H, Wright R, Brennand K, Pierce K, Eichenfield L, Pramparo T, Eyler L, Barnes C, Courchesne E, Geschwind D, Gage F, Wynshaw-Boris A, Muotri A. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Molecular Psychiatry 2016, 22: 820-835. PMID: 27378147, PMCID: PMC5215991, DOI: 10.1038/mp.2016.95.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsInsulin growth factor-1Pluripotent stem cellsTranscriptional cascadeNeuronal networksAutism spectrum disorderGrowth factor-1Human cell modelsNormal brain sizeEarly brain overgrowthPotential cellular mechanismsMolecular mechanismsGenetic studiesClinical trialsIGF-1Therapeutic effectBrain pathologyAbnormal neurogenesisΒ-cateninCellular mechanismsStem cellsBrain overgrowthProgenitor cellsNeural cellsAltered proliferation