2022
Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease
Brennand K. Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease. American Journal Of Psychiatry 2022, 179: 322-328. PMID: 35491564, DOI: 10.1176/appi.ajp.20220235.Commentaries, Editorials and LettersConceptsRisk variantsFunctional genomic studiesCell typesDiverse cell typesPatient-specific variantsStem cell modelGenomic studiesSignificant lociStem cell-based approachesGenetic studiesExciting questionsCell-based approachesEngineering strategiesGenetic profileNovel therapeutic interventionsCell modelPluripotent stem cell-based approachesVariantsComplex interplayGenetic riskCRISPRGenesLociBiologyTherapeutic interventions
2020
Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models
Gregory JA, Hoelzli E, Abdelaal R, Braine C, Cuevas M, Halpern M, Barretto N, Schrode N, Akbalik G, Kang K, Cheng E, Bowles K, Lotz S, Goderie S, Karch CM, Temple S, Goate A, Brennand KJ, Phatnani H. Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models. Cells 2020, 9: 1406. PMID: 32516938, PMCID: PMC7349756, DOI: 10.3390/cells9061406.Peer-Reviewed Original ResearchConceptsCell type-restricted expressionDisease-associated interactionsGene expression profilingHiPSC-derived motor neuronsHuman-induced pluripotent stem cellsPluripotent stem cellsCell-type specific perturbationsImmortalized cell linesRibosomal proteinsGenomic studiesExpression profilingMolecular mechanismsOff-target RNAMouse tissuesCell typesStem cellsPrimary mouse astrocytesExperimental replicatesCell linesMixed speciesMouse astrocytesExpressionMotor neuronsRiboTagCells
2019
CRISPR-based functional evaluation of schizophrenia risk variants
Rajarajan P, Flaherty E, Akbarian S, Brennand KJ. CRISPR-based functional evaluation of schizophrenia risk variants. Schizophrenia Research 2019, 217: 26-36. PMID: 31277978, PMCID: PMC6939156, DOI: 10.1016/j.schres.2019.06.017.Peer-Reviewed Original ResearchConceptsSchizophrenia-associated variantsPluripotent stem cellsCRISPR genome engineeringSchizophrenia risk variantsCellular functionsGenome engineeringGenomic studiesSchizophrenia lociList of variantsGene expressionPatient-specific humanGenotype dataRisk variantsStem cellsFunctional impactCommon variantsCRISPRPost-mortem brain tissueRecent findingsVariantsNeuropsychiatric diseasesPoint of convergenceGenetic riskLociSpecific effects
2016
Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease
Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand K, De Luca G, Crary J, Casaccia P, Buxbaum J, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B. Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease. Genome Medicine 2016, 8: 104. PMID: 27799057, PMCID: PMC5088659, DOI: 10.1186/s13073-016-0355-3.Peer-Reviewed Original ResearchConceptsGene expression changesCell type-specific marker genesExpression changesSingle-cell RNA-sequencing dataCo-expressed gene modulesLarge-scale gene expressionTranscriptomic network analysisCo-expression networkRNA-sequencing dataIntegrative network analysisNervous system developmentSelective regional vulnerabilityCritical molecular pathwaysActin cytoskeletonGenomic studiesGene modulesGenomic analysisGene expression abnormalitiesMarker genesMolecular basisGene expressionNetwork analysisMolecular mechanismsAxon guidanceMolecular pathways