2021
Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection
Dobrindt K, Hoagland DA, Seah C, Kassim B, O'Shea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Møller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports 2021, 16: 505-518. PMID: 33636110, PMCID: PMC7881728, DOI: 10.1016/j.stemcr.2021.02.010.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCOVID-19FemaleFurinGenetic Predisposition to DiseaseHost-Pathogen InteractionsHumansInduced Pluripotent Stem CellsMaleNeuronsPeptide HydrolasesPolymorphism, Single NucleotideSARS-CoV-2Vero CellsConceptsSARS-CoV-2Clinical complicationsSARS-CoV-2 infectionCommon genetic variationHigh-risk individualsHost genetic variantsSignificant interindividual variabilityNeuron infectionUnderlying comorbiditiesViral loadHealthy individualsViral infectionClinical heterogeneityVitro SusceptibilityEtiologic agentHost responseInterindividual variabilityDiscovery of drugsInfectionHost geneticsHuman induced pluripotent stem cellsSingle nucleotide polymorphismsAntibody repertoireMore diseasesComplications
2018
Expression-based drug screening of neural progenitor cells from individuals with schizophrenia
Readhead B, Hartley BJ, Eastwood BJ, Collier DA, Evans D, Farias R, He C, Hoffman G, Sklar P, Dudley JT, Schadt EE, Savić R, Brennand KJ. Expression-based drug screening of neural progenitor cells from individuals with schizophrenia. Nature Communications 2018, 9: 4412. PMID: 30356048, PMCID: PMC6200740, DOI: 10.1038/s41467-018-06515-4.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsHiPSC neural progenitor cellsCell typesCancer cell linesGene expression differencesProgenitor cellsDisease-associated genesPatient-specific platformPluripotent stem cellsTranscriptional responseExpression differencesTranscriptional signatureTranscriptomic signaturesStem cellsCell linesDependent mannerDrug discoveryDrug screeningCellsNeuropsychiatric disordersSchizophreniaBest treatmentDrugsDiscoveryGenes
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 cellsBrainComplicationsThe methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain
Jiang Y, Loh YE, Rajarajan P, Hirayama T, Liao W, Kassim BS, Javidfar B, Hartley BJ, Kleofas L, Park RB, Labonte B, Ho SM, Chandrasekaran S, Do C, Ramirez BR, Peter CJ, C W JT, Safaie BM, Morishita H, Roussos P, Nestler EJ, Schaefer A, Tycko B, Brennand KJ, Yagi T, Shen L, Akbarian S. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nature Genetics 2017, 49: 1239-1250. PMID: 28671686, PMCID: PMC5560095, DOI: 10.1038/ng.3906.Peer-Reviewed Original Research
2016
Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen
Xu M, Lee E, Wen Z, Cheng Y, Huang W, Qian X, TCW J, Kouznetsova J, Ogden S, Hammack C, Jacob F, Nguyen H, Itkin M, Hanna C, Shinn P, Allen C, Michael S, Simeonov A, Huang W, Christian K, Goate A, Brennand K, Huang R, Xia M, Ming G, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nature Medicine 2016, 22: 1101-1107. PMID: 27571349, PMCID: PMC5386783, DOI: 10.1038/nm.4184.Peer-Reviewed Original Research