Featured Publications
Patient-independent human induced pluripotent stem cell model: A new tool for rapid determination of genetic variant pathogenicity in long QT syndrome
Chavali NV, Kryshtal DO, Parikh SS, Wang L, Glazer AM, Blackwell DJ, Kroncke BM, Shoemaker MB, Knollmann BC. Patient-independent human induced pluripotent stem cell model: A new tool for rapid determination of genetic variant pathogenicity in long QT syndrome. Heart Rhythm 2019, 16: 1686-1695. PMID: 31004778, PMCID: PMC6935564, DOI: 10.1016/j.hrthm.2019.04.031.Peer-Reviewed Original ResearchConceptsLong QT syndromeExtracellular field potentialsQT syndromeHiPSC-CMGenetic testingPluripotent stem cell modelsHiPSC modelsSudden cardiac deathStem cell modelUnrelated healthy volunteersVentricular action potentialPatch-clamp studiesNovel missense variantVoltage-dependent inactivationCardiac deathClinical benefitCommercial genetic testingGenetic variant pathogenicityHealthy volunteersCell modelElectrophysiological propertiesAction potentialsBeating rateUnknown significancePatch clampThyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Parikh SS, Blackwell DJ, Gomez-Hurtado N, Frisk M, Wang L, Kim K, Dahl CP, Fiane A, Tønnessen T, Kryshtal DO, Louch WE, Knollmann BC. Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes. Circulation Research 2017, 121: 1323-1330. PMID: 28974554, PMCID: PMC5722667, DOI: 10.1161/circresaha.117.311920.Peer-Reviewed Original ResearchConceptsHuman-induced pluripotent stem cell-derived cardiomyocytesExcitation-contraction couplingPluripotent stem cell-derived cardiomyocytesCa releaseGlucocorticoid hormonesStem cell-derived cardiomyocytesCell-derived cardiomyocytesCa-induced Ca releaseT-tubule developmentAdult human ventricular cardiomyocytesExtensive T-tubule networkHuman ventricular cardiomyocytesL-type Ca channelsL-type CaT-tubulesIntracellular Ca releaseCell-based therapiesConfocal line scanHeart diseaseT-tubule networkFunctional maturationVentricular cardiomyocytesPermissive roleDay 16Ca channels
2017
Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes
Wang L, Kim K, Parikh S, Cadar AG, Bersell KR, He H, Pinto JR, Kryshtal DO, Knollmann BC. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes. Journal Of Molecular And Cellular Cardiology 2017, 114: 320-327. PMID: 29217433, PMCID: PMC5800960, DOI: 10.1016/j.yjmcc.2017.12.002.Peer-Reviewed Original ResearchConceptsMyofilament Ca sensitivityHiPSC-CMsControl hiPSC-CMsCa handlingTroponin TAction potentialsAction potential triangulationPro-arrhythmic changesCa sensitivityHuman ventricular action potentialCardiac troponin TAction potential changesIntracellular Ca transientsVentricular action potentialHuman iPSC-cardiomyocytesRod-shaped cardiomyocytesCardiac action potentialDiastolic dysfunctionImpaired relaxationSystolic functionVentricular arrhythmiasHypertrophic cardiomyopathySudden deathArrhythmia riskCardiac hypertrophyMyofilament Calcium-Buffering Dependent Action Potential Triangulation in Human-Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy
Wang L, Kryshtal DO, Kim K, Parikh S, Cadar AG, Bersell KR, He H, Pinto JR, Knollmann BC. Myofilament Calcium-Buffering Dependent Action Potential Triangulation in Human-Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy. Journal Of The American College Of Cardiology 2017, 70: 2600-2602. PMID: 29145956, PMCID: PMC5805484, DOI: 10.1016/j.jacc.2017.09.033.Peer-Reviewed Original Research