2022
Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease
Brennand K. Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease. American Journal Of Psychiatry 2022, 179: 322-328. PMID: 35491564, DOI: 10.1176/appi.ajp.20220235.Commentaries, Editorials and LettersMeSH KeywordsBrain DiseasesGenome-Wide Association StudyGenomicsHumansInduced Pluripotent Stem CellsMental DisordersConceptsRisk variantsFunctional genomic studiesCell typesDiverse cell typesPatient-specific variantsStem cell modelGenomic studiesSignificant lociStem cell-based approachesGenetic studiesExciting questionsCell-based approachesEngineering strategiesGenetic profileNovel therapeutic interventionsCell modelPluripotent stem cell-based approachesVariantsComplex interplayGenetic riskCRISPRGenesLociBiologyTherapeutic interventions
2020
Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics
Matos MR, Ho SM, Schrode N, Brennand KJ. Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics. Molecular And Cellular Neuroscience 2020, 107: 103532. PMID: 32712198, PMCID: PMC7484226, DOI: 10.1016/j.mcn.2020.103532.Peer-Reviewed Original ResearchConceptsPenetrant rare variantsDisease-associated variantsNeuronal cell typesPluripotent stem cellsGenomic engineeringFunctional characterizationComplex geneticsCRISPR engineeringCRISPR technologyIsogenic comparisonsPsychiatric genomicsCell typesGenetic variantsStem cellsIndividual variantsCommon variantsPolygenic disorderRare variantsVariantsComplex interplayGenomicsGenetic riskPleiotropyCRISPRGeneticsModeling the complex genetic architectures of brain disease
Fernando MB, Ahfeldt T, Brennand KJ. Modeling the complex genetic architectures of brain disease. Nature Genetics 2020, 52: 363-369. PMID: 32203467, PMCID: PMC7909729, DOI: 10.1038/s41588-020-0596-3.Peer-Reviewed Original ResearchConceptsGenetic architectureComplex genetic architectureFunctional validation studiesRelevant disease biologyIntersection of genomicsComplex genetic diseasesCombination of genesPluripotent stem cellsGene perturbationsIsogenic comparisonsMolecular mechanismsPhenotypic drug discoveryCell typesGenetic diseasesFunctional consequencesGenetic backgroundRisk variantsStem cellsCRISPRDisease biologyDrug discoveryRare variantsConfer riskGenetic diagnosisVariantsA computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles
Sey NYA, Hu B, Mah W, Fauni H, McAfee JC, Rajarajan P, Brennand KJ, Akbarian S, Won H. A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles. Nature Neuroscience 2020, 23: 583-593. PMID: 32152537, PMCID: PMC7131892, DOI: 10.1038/s41593-020-0603-0.Peer-Reviewed Original ResearchMeSH KeywordsBrainBrain DiseasesChromatinGenetic Predisposition to DiseaseGenomicsHumansPolymorphism, Single NucleotideRisk FactorsConceptsChromatin interaction profilesH-MAGMARisk genesMost risk variantsGenome-wide association studiesCell typesGene regulatory relationshipsRelevant target genesCell-type specificitySingle nucleotide polymorphism associationsBrain cell typesDisease-relevant tissuesInteraction profilesGenomic annotationsNearest geneTarget genesRegulatory relationshipsAssociation studiesBiological pathwaysGenesRisk variantsDevelopmental windowBiological mechanismsNeurodegenerative disordersHuman brain tissue
2017
Application 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 StatementsMeSH KeywordsBrainBrain DiseasesCRISPR-Cas SystemsGene EditingGene ExpressionHumansInduced Pluripotent Stem CellsConceptsCRISPR/Cas9 technologyPluripotent stem cellsTranscriptional regulatorsManipulation of DNAEpigenetic pathwaysGenomic editingSpecific lociCRISPR/Basic biologyCas9 technologyGene expressionStem cellsTargeted localizationEnzyme activityBrain developmentEpigenomeNeuropsychiatric diseasesGenomeCRISPRRepressionLociBiologyRegulatorEffectorsDNA
2015
Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders
Brennand KJ, Marchetto MC, Benvenisty N, Brüstle O, Ebert A, Belmonte J, Kaykas A, Lancaster MA, Livesey FJ, McConnell MJ, McKay RD, Morrow EM, Muotri AR, Panchision DM, Rubin LL, Sawa A, Soldner F, Song H, Studer L, Temple S, Vaccarino FM, Wu J, Vanderhaeghen P, Gage FH, Jaenisch R. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders. Stem Cell Reports 2015, 5: 933-945. PMID: 26610635, PMCID: PMC4881284, DOI: 10.1016/j.stemcr.2015.10.011.Peer-Reviewed Original ResearchMeSH KeywordsBrainBrain DiseasesDrug DiscoveryHumansInduced Pluripotent Stem CellsMosaicismNeurogenesisPrecision Medicine
2014
Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders
Hashimoto-Torii K, Torii M, Fujimoto M, Nakai A, Fatimy R, Mezger V, Ju MJ, Ishii S, Chao SH, Brennand KJ, Gage FH, Rakic P. Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders. Neuron 2014, 82: 560-572. PMID: 24726381, PMCID: PMC4051437, DOI: 10.1016/j.neuron.2014.03.002.Peer-Reviewed Original ResearchConceptsCerebral cortical cellsHuman neural progenitor cellsNeural progenitor cellsHeat shock factor 1Maternal seizuresSeizure susceptibilityPrenatal exposureNeuropsychiatric dysfunctionShock factor 1Neuronal responsesBrain cellsSchizophrenia patientsBrain disordersLate onsetMouse cortexStructural abnormalitiesNeuropsychiatric disordersHSF1 deficiencyExposure of embryosProgenitor cellsSubthreshold levelsFactor 1Induced pluripotent stem cellsEnvironmental insultsCortical cells