2023
29. GENE EXPRESSION ASSOCIATIONS WITH TRAUMA IN HUMAN POSTMORTEM BRAIN
Hicks E, Seah C, Cote A, Ciarcia J, Chakka A, Group T, Brennand K, Nestler E, Girgenti M, Huckins L. 29. GENE EXPRESSION ASSOCIATIONS WITH TRAUMA IN HUMAN POSTMORTEM BRAIN. European Neuropsychopharmacology 2023, 75: s72. DOI: 10.1016/j.euroneuro.2023.08.139.Peer-Reviewed Original ResearchMajor depressive disorderPost-traumatic stress disorderHuman postmortem brainPostmortem brainsPsychiatric disordersNeurobiological consequencesTranscriptional signatureMajor precipitating factorEarly life stressCase/control statusGene expression associationsType of traumaStress-related disordersTrauma measuresTrauma-exposed individualsTraumatic Stress DisorderExpression associationsBrain donorsDepressive disorderMale miceFrontal cortexPrecipitating factorsMouse modelAnimal modelsPsychosocial stress
2022
Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome
Fulton S, Wenderski W, Lepack A, Eagle A, Fanutza T, Bastle R, Ramakrishnan A, Hays E, Neal A, Bendl J, Farrelly L, Al-Kachak A, Lyu Y, Cetin B, Chan J, Tran T, Neve R, Roper R, Brennand K, Roussos P, Schimenti J, Friedman A, Shen L, Blitzer R, Robison A, Crabtree G, Maze I. Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome. Nature Communications 2022, 13: 6384. PMID: 36289231, PMCID: PMC9606253, DOI: 10.1038/s41467-022-34200-0.Peer-Reviewed Original ResearchConceptsGene expressionChromatin accessibilityChromatin effectorsBAF chromatinGenetic basisTrisomic animalsIPS cellsBRWD1Chromosome 21Down syndromeHSA21Ts65Dn mouse modelCommon chromosomal conditionExpressionChromatinNormal neurodevelopmentChromosomal conditionHippocampal LTPMouse modelMistargetingGenesTrisomic miceCognitive deficitsEffectorsSyndrome
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
2017
High-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
Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models
Xu J, Hartley BJ, Kurup P, Phillips A, Topol A, Xu M, Ononenyi C, Foscue E, Ho SM, Baguley TD, Carty N, Barros CS, Müller U, Gupta S, Gochman P, Rapoport J, Ellman JA, Pittenger C, Aronow B, Nairn AC, Nestor MW, Lombroso PJ, Brennand KJ. Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models. Molecular Psychiatry 2016, 23: 271-281. PMID: 27752082, PMCID: PMC5395367, DOI: 10.1038/mp.2016.163.Peer-Reviewed Original ResearchConceptsBrain-specific tyrosine phosphataseDephosphorylation of GluN2BExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Glutamate receptor internalizationPluripotent stem cellsKnockout mouse modelTyrosine phosphataseMouse modelKinase 1/2Receptor internalizationImportant regulatorGenetic reductionLoss of NMDARsStem cellsN-methyl DPharmacological inhibitionProtein levelsSynaptic functionSTEP61Patient cohortForebrain neuronsBehavioral deficitsExcitatory neuronsSchizophrenia model
2015
Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms
Flaherty E, Brennand K. Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms. Brain Research 2015, 1655: 283-293. PMID: 26581337, PMCID: PMC4865445, DOI: 10.1016/j.brainres.2015.11.009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCopy number variationsIsogenic hiPSC linesRare variantsFull genetic architectureGenome editing technologyPluripotent stem cellsStrong heritable componentPatient-derived humanGenetic architectureEditing technologyHeritable componentBehavioral defectsNumber variationsNew therapeutic targetsHiPSC linesGenetic backgroundStem cellsCommon variantsFunctional contributionDisease mechanismsSingle variantMouse modelHigh penetranceHiPSCsTherapeutic target