2020
Modeling the complex genetic architectures of brain disease
Fernando MB, Ahfeldt T, Brennand KJ. Modeling the complex genetic architectures of brain disease. Nature Genetics 2020, 52: 363-369. PMID: 32203467, PMCID: PMC7909729, DOI: 10.1038/s41588-020-0596-3.Peer-Reviewed Original ResearchConceptsGenetic architectureComplex genetic architectureFunctional validation studiesRelevant disease biologyIntersection of genomicsComplex genetic diseasesCombination of genesPluripotent stem cellsGene perturbationsIsogenic comparisonsMolecular mechanismsPhenotypic drug discoveryCell typesGenetic diseasesFunctional consequencesGenetic backgroundRisk variantsStem cellsCRISPRDisease biologyDrug discoveryRare variantsConfer riskGenetic diagnosisVariants
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
2014
Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
Schadt E, Buchanan S, Brennand K, Merchant K. Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders. Frontiers In Pharmacology 2014, 5: 252. PMID: 25520658, PMCID: PMC4251289, DOI: 10.3389/fphar.2014.00252.Peer-Reviewed Original ResearchBiology approachNeurological disease pathwaysSpecific neural cell typesSystems biology approachPatient-derived hiPSCsDrug discoveryGeneration of hiPSCsInduced pluripotent stem cellsRepresentative neurological diseasesHuman induced pluripotent stem cellsNeural cell typesPluripotent stem cellsSingle geneGlobal epigeneticExpression studiesFrequent clinical failuresDrug screening strategiesNeurodegenerative diseases Alzheimer's diseaseHuman diseasesPsychiatric disorders schizophreniaCell typesCNS disordersHiPSC linesDisease pathwaysBiological networks