2021
Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies
Mishra H, Ying N, Luis A, Wei H, Nguyen M, Nakhla T, Vandenburgh S, Alda M, Berrettini W, Brennand K, Calabrese J, Coryell W, Frye M, Gage F, Gershon E, McInnis M, Nievergelt C, Nurnberger J, Shilling P, Oedegaard K, Zandi P, Kelsoe J, Welsh D, McCarthy M. Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies. Molecular Psychiatry 2021, 26: 3383-3394. PMID: 33674753, PMCID: PMC8418615, DOI: 10.1038/s41380-021-01048-7.Peer-Reviewed Original ResearchConceptsNeuronal precursor cellsBipolar disorderCircadian rhythm abnormalitiesRhythm abnormalitiesBD groupCircadian rhythmPatient-derived neuronsMania/hypomaniaExpression of Per2Induced pluripotent stem cellsPER2 protein levelsGlutamatergic neuronsRecurrent episodesBD patientsControl neuronsLithium respondersEffective drugsNeuropsychiatric illnessLithium responsivenessPatient neuronsNeuronsLithium responseProtein levelsRhythm deficitsPrecursor cells
2018
GJA1 (connexin43) is a key regulator of Alzheimer’s disease pathogenesis
Kajiwara Y, Wang E, Wang M, Sin WC, Brennand KJ, Schadt E, Naus CC, Buxbaum J, Zhang B. GJA1 (connexin43) is a key regulator of Alzheimer’s disease pathogenesis. Acta Neuropathologica Communications 2018, 6: 144. PMID: 30577786, PMCID: PMC6303945, DOI: 10.1186/s40478-018-0642-x.Peer-Reviewed Original ResearchConceptsPost-mortem Alzheimer's diseaseAlzheimer's diseaseTop key driverRNA sequencing analysisDisease pathogenesisProteomic datasetsKey regulatorNormal control brainsGJA1 expressionAlzheimer's disease (AD) pathogenesisApoE protein levelsPromising pharmacological targetSequencing analysisGJA1Wildtype astrocytesWildtype neuronsAβ metabolismAβ phagocytosisProtein levelsControl brainsAD pathogenesisAD amyloidPharmacological targetsAstrocytesCognitive function
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
Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients
Topol A, English J, Flaherty E, Rajarajan P, Hartley B, Gupta S, Desland F, Zhu S, Goff T, Friedman L, Rapoport J, Felsenfeld D, Cagney G, Mackay-Sim A, Savas J, Aronow B, Fang G, Zhang B, Cotter D, Brennand K. Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients. Translational Psychiatry 2015, 5: e662-e662. PMID: 26485546, PMCID: PMC4930118, DOI: 10.1038/tp.2015.118.Peer-Reviewed Original ResearchConceptsHiPSC neural progenitor cellsNeural progenitor cellsNovel post-transcriptional mechanismProtein synthesisGlobal protein translationElongation factor proteinGlobal protein synthesisPost-transcriptional mechanismsProgenitor cellsHuman-induced pluripotent stem cellsPluripotent stem cellsMass spectrometry evidenceTranslation machineryTranslation initiationProtein translationEpigenetic factorsFactor proteinStem cellsProtein levelsTotal protein levelsCellsUnaffected controlsMachineryProteinAbundance