2024
F91. MAPPING THE EFFECTS OF OPIOID USE DISORDER GENETIC ASSOCIATED VARIANTS IN BRAIN PATHWAYS AT A SINGLE CELL LEVEL
Rivera-Hernández M, Martínez-Magaña J, Brennand K, Montalvo-Ortiz J. F91. MAPPING THE EFFECTS OF OPIOID USE DISORDER GENETIC ASSOCIATED VARIANTS IN BRAIN PATHWAYS AT A SINGLE CELL LEVEL. European Neuropsychopharmacology 2024, 87: 254. DOI: 10.1016/j.euroneuro.2024.08.502.Peer-Reviewed Original ResearchOpioid use disorderDopaminergic neuronsReward-related learningOrbital frontal cortexGenetic variantsFunction of dopaminergic neuronsMap genetic variantsGenome-wide studiesCell projection organizationSingle-cell expression profilesCell typesOxytocin signaling pathwayPrefrontal cortexMotivated behaviorFrontal cortexDopaminergic pathwaysUse disorderBrain regionsModulation of chemical synaptic transmissionStriatumSingle-cell RNAseqCell-specific pathwaysBehavioral responsesScRNA-seqStriatum cells
2023
STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD
Seah C, Signer R, Young H, Kozik E, Rusielewicz T, Bader H, Xu C, de Pins A, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD. European Neuropsychopharmacology 2023, 75: s40. DOI: 10.1016/j.euroneuro.2023.08.081.Peer-Reviewed Original ResearchCommon genetic variationGenetic variationStress responseCell typesEQTL associationsTranscriptional stress responseGenomic risk lociTissue-specific mannerChIP-seq datasetsCell type deconvolutionCommon genetic variantsPost-mortem brainsGene expression signaturesHiPSC-derived neuronsTranscription factorsSuch lociCatalog genesRisk lociGenetic studiesExpression signaturesGenetic variantsRegulatory activityGenesEQTLsMechanistic understanding
2021
Applying stem cells and CRISPR engineering to uncover the etiology of schizophrenia
Michael Deans P, Brennand K. Applying stem cells and CRISPR engineering to uncover the etiology of schizophrenia. Current Opinion In Neurobiology 2021, 69: 193-201. PMID: 34010781, PMCID: PMC8387340, DOI: 10.1016/j.conb.2021.04.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCell type-specific fashionStem cell biologyType-specific fashionDisease-associated variantsNeural cell typesCommon genetic variantsMore genesCell biologyCRISPR engineeringGene manipulationGene targetsCRISPR technologyMolecular geneticsInvaluable advancesCell typesHiPSC technologyGenetic variantsStem cellsIndividual variantsEtiology of diseasePolygenic disorderVariantsComplex interactionsRecent advancesEtiology of schizophreniaAnalysis 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
Parsing the Functional Impact of Noncoding Genetic Variants in the Brain Epigenome
Powell SK, O'Shea C, Brennand KJ, Akbarian S. Parsing the Functional Impact of Noncoding Genetic Variants in the Brain Epigenome. Biological Psychiatry 2020, 89: 65-75. PMID: 33131715, PMCID: PMC7718420, DOI: 10.1016/j.biopsych.2020.06.033.Peer-Reviewed Original ResearchConceptsGenetic variantsDisease-associated genetic variationProtein-coding lociRisk-associated genetic variantsGene regulatory lociThousands of variantsFunctional impactRare genetic variantsEpigenomic mappingRegulatory lociBrain epigenomeGenetic variationDNA sequencesNoncoding variantsGene expressionIntegrative analysisEpigenomic architectureMolecular pathwaysPsychiatric geneticsFunctional readoutRisk variantsLociVariantsHighlight findingsEpigenomeIntegration 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 riskPleiotropyCRISPRGenetics
2013
Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells
Brennand K, Landek-Salgado M, Sawa A. Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells. Biological Psychiatry 2013, 75: 936-944. PMID: 24331955, PMCID: PMC4022707, DOI: 10.1016/j.biopsych.2013.10.025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCommon clinical manifestationsSmall patient cohortPathology of schizophreniaStem cellsPluripotent stem cellsComplex genetic conditionClinical manifestationsPatient cohortClinical etiologyHuman neuronsAnimal modelsClinical heterogeneityHeterogeneous patientsClinical diagnosisSchizophreniaGenetic conditionsMental conditionPatientsGenetic variantsBiological mechanismsClinical constraintsRare genetic variantsCellsCohortEtiology