2022
Modeling 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 ResearchMeSH KeywordsGene ExpressionGene-Environment InteractionGlucocorticoidsHumansInduced Pluripotent Stem CellsLeukocytes, MononuclearNeuronsStress Disorders, Post-TraumaticConceptsPost-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 veteransStem Cell Models for Context-Specific Modeling in Psychiatric Disorders
Seah C, Huckins L, Brennand K. Stem Cell Models for Context-Specific Modeling in Psychiatric Disorders. Biological Psychiatry 2022, 93: 642-650. PMID: 36658083, DOI: 10.1016/j.biopsych.2022.09.033.Peer-Reviewed Original ResearchMeSH KeywordsGene Expression RegulationGenome-Wide Association StudyHumansInduced Pluripotent Stem CellsMental DisordersQuantitative Trait LociConceptsStem cell modelCell typesTarget genesGenome-wide association study (GWAS) lociExpression quantitative trait lociGenome-wide association studiesParallel reporter assaysQuantitative trait lociStem cell-derived cell typesPluripotent stem cell modelsComplex polygenic architectureContext-specific mannerPsychiatric disorder riskTrait lociRegulates transcriptionStudy lociGenetic regulationPolygenic architectureCRISPR screensCell modelCausal variantsRegulated expressionPatient-specific humanReporter assaysAssociation studies
2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchMeSH KeywordsAutism Spectrum DisorderDopaminergic NeuronsHumansInduced Pluripotent Stem CellsMesencephalonReproducibility of ResultsConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populations
2020
Massively parallel techniques for cataloguing the regulome of the human brain
Townsley KG, Brennand KJ, Huckins LM. Massively parallel techniques for cataloguing the regulome of the human brain. Nature Neuroscience 2020, 23: 1509-1521. PMID: 33199899, PMCID: PMC8018778, DOI: 10.1038/s41593-020-00740-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBrainClustered Regularly Interspaced Short Palindromic RepeatsGene Expression RegulationGeneticsHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsRegulatory Elements, TranscriptionalConceptsRegulatory elementsTarget genesParallel reporter assaysPutative regulatory elementsNon-coding regionsDisease-associated lociSpecific expression patternsCandidate risk lociPluripotent stem cellsHigh-throughput assaysRelevant molecular pathwaysTranscriptional responseRegulatory architectureRisk lociExpression patternsReporter assaysComplex brain disordersMolecular pathwaysRegulomeStem cellsRisk architectureGenetic riskGenesLociGenetic diagnosis
2019
Synergistic effects of common schizophrenia risk variants
Schrode N, Ho SM, Yamamuro K, Dobbyn A, Huckins L, Matos MR, Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics 2019, 51: 1475-1485. PMID: 31548722, PMCID: PMC6778520, DOI: 10.1038/s41588-019-0497-5.Peer-Reviewed Original ResearchMeSH KeywordsChloride ChannelsCRISPR-Cas SystemsFemaleFurinGene EditingGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInduced Pluripotent Stem CellsMaleMonomeric Clathrin Assembly ProteinsPolymorphism, Single NucleotideQuantitative Trait LociSchizophreniaSNARE ProteinsConceptsExpression quantitative trait lociComplex genetic disorderEQTL genesCommon variantsQuantitative trait lociRisk variantsGene expression differencesPsychiatric disease riskCommon risk variantsPluripotent stem cellsSchizophrenia risk variantsGenetic disordersTrait lociGene perturbationsGenetic approachesExpression differencesGene editingStem cellsGeneralizable phenomenonSynaptic functionGenesVariantsCRISPRLociSpecific effects