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 cells42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS
Seah C, Signer R, Young H, Hicks E, Rusielewicz T, Bader H, Xu C, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. 42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS. European Neuropsychopharmacology 2024, 87: 71-72. DOI: 10.1016/j.euroneuro.2024.08.156.Peer-Reviewed Original ResearchPost-mortem brainsTranscription factor binding sitesAbsence of cellular stressCombat-exposed veteransFactor binding sitesImpact gene expressionBinding sitesGR binding sitesPositive regulatory activityMotif enrichmentSequence readsCRISPRi screenOpen chromatinFunctional annotationBrain regionsTraumatic stressCRISPR screensEQTLTraumatic experiencesLeading locusPTSDPerturbed genesRegulatory architectureTranscriptomic activityTranscriptomic response
2021
Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets
Neff R, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Wang E, Horgusluoglu-Moloch E, Song W, Li A, Castranio E, Julia T, Ho L, Goate A, Fossati V, Noggle S, Gandy S, Ehrlich M, Katsel P, Schadt E, Cai D, Brennand K, Haroutunian V, Zhang B. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Science Advances 2021, 7: eabb5398. PMID: 33523961, PMCID: PMC7787497, DOI: 10.1126/sciadv.abb5398.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseMouse modelAD mouse modelDiverse pathophysiologic mechanismsTau-mediated neurodegenerationMajor molecular subtypesSpecific mouse modelsPathophysiologic mechanismsHuman trialsMolecular subtypesImmune activityHeterogeneous diseaseAD cohortAD subtypesBrain regionsSynaptic signalingMolecular subtypingSubtype heterogeneityDiseaseCommon formPrecision medicineMultiscale network analysisDevastating diseaseMolecular heterogeneitySubtypes
2020
Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanisms
2014
Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells
Yu D, Di Giorgio F, Yao J, Marchetto M, Brennand K, Wright R, Mei A, Mchenry L, Lisuk D, Grasmick J, Silberman P, Silberman G, Jappelli R, Gage F. Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells. Stem Cell Reports 2014, 2: 295-310. PMID: 24672753, PMCID: PMC3964286, DOI: 10.1016/j.stemcr.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsCell DifferentiationDentate GyrusElectrophysiological PhenomenaEmbryoid BodiesGene ExpressionGenes, ReporterHippocampusHomeodomain ProteinsHumansNerve NetNeural Stem CellsNeurogenesisNeuronsNeurotransmitter AgentsPluripotent Stem CellsPyramidal CellsSchizophreniaTumor Suppressor ProteinsConceptsHippocampal neurogenesisDentate gyrusHippocampal dentate gyrusDG granule neuronsStem cellsPluripotent stem cellsSpontaneous neurotransmitter releaseNeuronal network maturationPatient-derived humanHuman pluripotent stem cellsDifferentiation paradigmNeuronal activityGranule neuronsBrain regionsNeurotransmitter releaseNeurodevelopmental aspectsLineage-specific cellsNeurogenesisNeuronsNetwork maturationReduced levelsPersonalized medicineHuman diseasesCellsDrug screening
2012
Modeling Schizophrenia Using Induced Pluripotent Stem Cell–Derived and Fibroblast-Induced Neurons
Tran N, Ladran I, Brennand K. Modeling Schizophrenia Using Induced Pluripotent Stem Cell–Derived and Fibroblast-Induced Neurons. Schizophrenia Bulletin 2012, 39: 4-10. PMID: 23172000, PMCID: PMC3523925, DOI: 10.1093/schbul/sbs127.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsModeling psychiatric disorders at the cellular and network levels
Brennand K, Simone A, Tran N, Gage F. Modeling psychiatric disorders at the cellular and network levels. Molecular Psychiatry 2012, 17: 1239-1253. PMID: 22472874, PMCID: PMC3465628, DOI: 10.1038/mp.2012.20.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCell-based studiesPluripotent stem cell-derived neuronsStem cell-derived neuronsLive human neuronsCell-derived neuronsPsychiatric disordersBasic phenotypesGenetic backgroundHuman neuronsClinical symptomsComplex arrayBipolar disorderBrain regionsDisease statesNeuronsSingle neuronsDisordersLimitless numberAutism spectrum disorderSpectrum disorderPhenotypeFibroblastsPatientsSymptomsSchizophrenia