2025
Combinatorial therapy regimens targeting preclinical models of melanoma resistant to immune checkpoint blockade
Khan I, Rodriguez-Brotons A, Bhattacharjee A, Bezrookove V, Dar A, De Semir D, Nosrati M, Ice R, Soroceanu L, Leong S, Kim K, Shi Y, Cleaver J, Miller J, Desprez P, Kirkwood J, Bosenberg M, Salomonis N, McAllister S, Kashani-Sabet M. Combinatorial therapy regimens targeting preclinical models of melanoma resistant to immune checkpoint blockade. Journal Of Clinical Investigation 2025, 135 PMID: 40638246, DOI: 10.1172/jci185220.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeResistance to immune checkpoint blockadeCheckpoint blockadePreclinical modelsHigh-throughput drug screeningPatient-derived xenograft modelsCombination of cobimetinibCombinatorial therapy regimensT cell infiltrationAntigen presentation machineryEffective therapeutic optionClinical trial designModalities in vivoDrug screeningPresentation machineryImmunocompetent modelMelanoma subtypesTherapy regimensCombinatorial regimensPreclinical efficacyTherapeutic optionsMurine modelTherapeutic vulnerabilitiesXenograft modelDrug combinationsHigh-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Effraim P, Dib-Hajj S, Waxman S. High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons. Nature Protocols 2025, 1-26. PMID: 40514421, DOI: 10.1038/s41596-025-01194-0.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp methodPatch-clamp approachPatch-clamp experimentsHeterologous cell linesIsolated neuronsInvestigated receptorsGraphical user interfaceIsolation of neuronsCell preparationsExcitable cellsOpen-source softwareCell linesNeuronsFiltration criteriaIndividual neuronsUser interfaceNative stateDrug screeningRobotic systemDrug developmentManual implementationBiophysical equationsComplex datasetsIntact tissueAdvancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches
Lu Y, Liu Y, Yan Y, Fooladi S, Qyang Y. Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches. Biophysical Reviews 2025, 17: 169-183. PMID: 40060015, PMCID: PMC11885779, DOI: 10.1007/s12551-024-01267-6.Peer-Reviewed Original ResearchHuman induced pluripotent stem cell-derived cardiomyocytesMaturity of human-induced pluripotent stem cell-derived cardiomyocytesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesIon channel expressionCell-derived cardiomyocytesChannel expressionCo-culture systemElectrophysiological propertiesAdult cardiomyocytesCardiomyocyte maturationSynchronous contractionProtein expressionGrowth factorSarcomere alignmentClinical practiceElectrical pacingElectrical stimulation techniquesMaturation protocolsCardiomyocytesCo-CultureRegenerative medicineElectrical stimulation approachesDisease modelsDrug screening
2024
Engineered heart tissue: Design considerations and the state of the art
Gokhan I, Blum T, Campbell S. Engineered heart tissue: Design considerations and the state of the art. Biophysics Reviews 2024, 5: 021308. PMID: 38912258, PMCID: PMC11192576, DOI: 10.1063/5.0202724.Peer-Reviewed Original Research
2023
Methamphetamine-Associated Catatonia: Case Series and Systematic Review of the Literature from 1943-2020
Slavnic B, Barnett B, McIntire S, Becker R, Saba S, Vellanki K, Honaker L, Weleff J, Carroll B. Methamphetamine-Associated Catatonia: Case Series and Systematic Review of the Literature from 1943-2020. Annals Of Clinical Psychiatry 2023, 35: 167-177. PMID: 37459499, DOI: 10.12788/acp.0116.Peer-Reviewed Original ResearchConceptsAssociated with catatoniaCatatonia Rating ScaleMethamphetamine useGeneral medical conditionsCase seriesBush-Francis Catatonia Rating ScaleSystematic reviewUrine drug screensMedical conditionsRating ScaleCases of catatoniaDSM-5 criteriaShorter hospitalDopamine functionCatatonic patientsCatatoniaDSM-5MethamphetaminePatientsNeural mechanismsSubstance intoxicationDrug screeningHospitalReviewLorazepamHigh-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
2022
Development of patient derived organoids for cancer drug screening applications
Baskar G, Palaniyandi T, Viswanathan S, Rajendran B, Ravi M, Sivaji A. Development of patient derived organoids for cancer drug screening applications. Acta Histochemica 2022, 124: 151895. PMID: 35486967, DOI: 10.1016/j.acthis.2022.151895.Peer-Reviewed Original ResearchConceptsPre-clinical modelsEx vivo tissue cultureDevelopment of patientsCancer researchStem cellsVivo tissue culturePatient responseAbnormal cell growthProgenitor cellsHigh-throughput drug screeningVivo propertiesOrganoidsHuman organoidsPluripotent stem cellsCell growthDrug screening applicationsDrug screeningThroughput drug screeningEmbryonic stem cellsTissueCellsTissue cultureEffective recapitulationPatientsClinic
2019
Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells
Chioccioli M, Feriani L, Kotar J, Bratcher PE, Cicuta P. Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells. Nature Communications 2019, 10: 1763. PMID: 30992452, PMCID: PMC6467870, DOI: 10.1038/s41467-019-09798-3.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial cellsCystic fibrosis respiratory epithelial cellsAirway epithelial cellsRespiratory epithelial cellsCiliary beat frequencyCiliary beatingRespiratory disordersRespiratory diseaseClinical observationsCystic fibrosisDrug efficacyPilot studyDrug testingEfficient drugsDrugsIndividual donorsEfficacyDrug screeningBeat dynamicsCellsSame genotypeFibrosisDonorsDisease
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
The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening
Gonzalez D, Gregory J, Brennand K. The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening. Frontiers In Cell And Developmental Biology 2017, 5: 117. PMID: 29312938, PMCID: PMC5742170, DOI: 10.3389/fcell.2017.00117.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsLovastatin suppresses hyperexcitability and seizure in Angelman syndrome model
Chung L, Bey AL, Towers AJ, Cao X, Kim IH, Jiang YH. Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model. Neurobiology Of Disease 2017, 110: 12-19. PMID: 29097328, PMCID: PMC5903876, DOI: 10.1016/j.nbd.2017.10.016.Peer-Reviewed Original ResearchConceptsEpileptiform activityMouse modelAngelman syndrome modelFragile X syndrome mouse modelLower seizure thresholdSyndrome mouse modelNeural mechanismsAngelman syndromeSeizure thresholdSynaptic dysfunctionAudiogenic seizuresExcitatory neurotransmissionLocal circuitsSyndrome modelSeizuresUBE3ADrug screeningFXS modelsHyperexcitabilitySupDysfunctionEpilepsyNeurotransmissionSyndromeDissection
2016
Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells
Dash BC, Levi K, Schwan J, Luo J, Bartulos O, Wu H, Qiu C, Yi T, Ren Y, Campbell S, Rolle MW, Qyang Y. Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells. Stem Cell Reports 2016, 7: 19-28. PMID: 27411102, PMCID: PMC4945325, DOI: 10.1016/j.stemcr.2016.05.004.Peer-Reviewed Original ResearchConceptsVascular tissue engineeringFunctional vascular smooth muscle cellsCell-based tissueSelf-assembly approachRenewable sourcesTissue engineeringPluripotent stem cellsPlatform technologyBiomedical applicationsTissue ringsDrug screeningDisease modelingTissue model systemsHuman iPSCStem cellsBroad utilityEfficient approachLarge quantitiesEngineeringMaterials
2015
Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells
Ho S, Hartley B, Julia T, Beaumont M, Stafford K, Slesinger P, Brennand K. Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods 2015, 101: 113-124. PMID: 26626326, PMCID: PMC4860098, DOI: 10.1016/j.ymeth.2015.11.019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsNeural progenitor cellsHiPSC-derived neural progenitor cellsHigh-throughput drug screeningHiPSC neural progenitor cellsExogenous transcription factorsProgenitor cellsInduced pluripotent stem cellsPatient-specific platformPluripotent stem cellsPatient-derived neuronsSomatic reprogrammingTranscription factorsGenetic variationExcitatory neuronsDrug screeningNeurogenin 2Neuronal inductionFunctional neuronsThroughput drug screeningNeuronal phenotypeLentiviral transductionStem cellsStarting populationDisease etiology
2014
Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells
Yu D, Di Giorgio F, Yao J, Marchetto M, Brennand K, Wright R, Mei A, Mchenry L, Lisuk D, Grasmick J, Silberman P, Silberman G, Jappelli R, Gage F. Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells. Stem Cell Reports 2014, 2: 295-310. PMID: 24672753, PMCID: PMC3964286, DOI: 10.1016/j.stemcr.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsCell DifferentiationDentate GyrusElectrophysiological PhenomenaEmbryoid BodiesGene ExpressionGenes, ReporterHippocampusHomeodomain ProteinsHumansNerve NetNeural Stem CellsNeurogenesisNeuronsNeurotransmitter AgentsPluripotent Stem CellsPyramidal CellsSchizophreniaTumor Suppressor ProteinsConceptsHippocampal neurogenesisDentate gyrusHippocampal dentate gyrusDG granule neuronsStem cellsPluripotent stem cellsSpontaneous neurotransmitter releaseNeuronal network maturationPatient-derived humanHuman pluripotent stem cellsDifferentiation paradigmNeuronal activityGranule neuronsBrain regionsNeurotransmitter releaseNeurodevelopmental aspectsLineage-specific cellsNeurogenesisNeuronsNetwork maturationReduced levelsPersonalized medicineHuman diseasesCellsDrug screening
2013
Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening
Held MA, Langdon CG, Platt JT, Graham-Steed T, Liu Z, Chakraborty A, Bacchiocchi A, Koo A, Haskins JW, Bosenberg MW, Stern DF. Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening. Cancer Discovery 2013, 3: 52-67. PMID: 23239741, PMCID: PMC3546137, DOI: 10.1158/2159-8290.cd-12-0408.Peer-Reviewed Original ResearchConceptsMutant BRAF melanomaCyclin-dependent kinase inhibitorBRAF melanomaSmall molecule inhibitorsHigh-throughput drug screeningDrug screeningEGF receptorCombination therapyDrug combinationsMelanoma culturesContext of genotypePairwise combinationsResistance phenotypeCombinatorial drug screeningUnique treatment regimensCombination of statinsVivo xenograftsKinase inhibitorsMutant BRAFMutationsEfficacious drug combinationsPartial responseTreatment regimensRas mutationsBRAF mutations
2012
Excision of a Viral Reprogramming Cassette by Delivery of Synthetic Cre mRNA
Loh Y, Yang JC, De Los Angeles A, Guo C, Cherry A, Rossi DJ, Park I, Daley GQ. Excision of a Viral Reprogramming Cassette by Delivery of Synthetic Cre mRNA. Current Protocols In Stem Cell Biology 2012, 21: 4a.5.1-4a.5.16. PMID: 22605648, PMCID: PMC3397830, DOI: 10.1002/9780470151808.sc04a05s21.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsTransgene-free methodsHuman iPS cellsResidual transgene expressionPatient-specific induced pluripotent stem cellsIPS cellsInduced pluripotent stem cellsStem cellsTransgene expressionFree humanHuman OCT4MRNA transfectionDrug screeningProtein transductionCre mRNADifferentiation potentialCell therapySingle vectorLow efficiencyCassetteRetroviral transfectionCre recombinaseEfficiencyTransfectionExperimental generationHuman induced pluripotent stem cells and neurodegenerative disease
Jung YW, Hysolli E, Kim KY, Tanaka Y, Park IH. Human induced pluripotent stem cells and neurodegenerative disease. Current Opinion In Neurology 2012, 25: 125-130. PMID: 22357218, PMCID: PMC3786112, DOI: 10.1097/wco.0b013e3283518226.Peer-Reviewed Original ResearchConceptsNeurodegenerative diseasesReplacement therapyCell replacement therapyParkinson's diseasePositive therapeutic effectDisease modelsParkinson's disease modelAmyotrophic lateral sclerosisNeuron-specific transcription factorSpinal muscular atrophyStem cellsDrug screeningDopaminergic neuronsIntermediate cell typeTherapeutic effectEffective treatmentLateral sclerosisDisease-specific iPSCsMuscular atrophyAlzheimer's diseaseNeurodegenerative disordersCellular therapyDiseaseTherapyHuman induced pluripotent stem cells
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