Featured Publications
Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2
Wleklinski M, Kryshtal D, Kim K, Parikh S, Blackwell D, Marty I, Iyer V, Knollmann B. Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2. Circulation Research 2022, 131: 673-686. PMID: 36102198, PMCID: PMC9529867, DOI: 10.1161/circresaha.121.320661.Peer-Reviewed Original ResearchThyroid 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
2023
Regulation of Postnatal Cardiomyocyte Maturation by an RNA Splicing Regulator RBFox1
Huang J, Lee J, Rau C, Pezhouman A, Yokota T, Miwa H, Feldman M, Kong T, Yang Z, Tay W, Pushkarsky I, Kim K, Parikh S, Udani S, Soh B, Gao C, Stiles L, Shirihai O, Knollmann B, Ardehali R, Di Carlo D, Wang Y. Regulation of Postnatal Cardiomyocyte Maturation by an RNA Splicing Regulator RBFox1. Circulation 2023, 148: 1263-1266. PMID: 37844148, PMCID: PMC10593507, DOI: 10.1161/circulationaha.122.061602.Peer-Reviewed Original Research
2022
Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization
Bersell K, Yang T, Mosley J, Glazer A, Hale A, Kryshtal D, Kim K, Steimle J, Brown J, Salem J, Campbell C, Hong C, Wells Q, Johnson A, Short L, Blair M, Behr E, Petropoulou E, Jamshidi Y, Benson M, Keyes M, Ngo D, Vasan R, Yang Q, Gerszten R, Shaffer C, Parikh S, Sheng Q, Kannankeril P, Moskowitz I, York J, Wang T, Knollmann B, Roden D. Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization. Circulation 2022, 147: 824-840. PMID: 36524479, PMCID: PMC9992308, DOI: 10.1161/circulationaha.122.062193.Peer-Reviewed Original ResearchConceptsPlatelet-derived growth factorInduced pluripotent stem cellsBrugada syndromeArrhythmia syndromesSerum platelet-derived growth factorSodium currentGeneral transcriptional mechanismFramingham Heart Study cohortPI3KPDGF receptor expressionLate sodium currentCardiac sodium currentCardiac transcription factorsSmall molecule perturbationsCurrent-clamp experimentsCardiac sodium channel geneSodium channel geneFramingham Heart StudyMurine model systemPluripotent stem cellsMonogenic arrhythmia syndromesReceptor blockadeElectrophysiologic abnormalitiesQTc intervalStudy cohort
2018
Cardiomyocyte-specific deletion of GSK-3β leads to cardiac dysfunction in a diet induced obesity model
Gupte M, Tumuluru S, Sui JY, Singh AP, Umbarkar P, Parikh SS, Ahmad F, Zhang Q, Force T, Lal H. Cardiomyocyte-specific deletion of GSK-3β leads to cardiac dysfunction in a diet induced obesity model. International Journal Of Cardiology 2018, 259: 145-152. PMID: 29398139, PMCID: PMC5869114, DOI: 10.1016/j.ijcard.2018.01.013.Peer-Reviewed Original ResearchConceptsHigh-fat dietAdverse ventricular remodelingCardiac dysfunctionCardiac functionVentricular remodelingBody weightGSK-3βControl dietHeart weight/tibia lengthDiet-induced cardiac dysfunctionIndependent risk factorImpaired cardiac functionSevere cardiac dysfunctionFat mass compositionLittermate control miceProtective compensatory mechanismCardiomyocyte-specific deletionComparable body weightTibia lengthTransthoracic echocardiographyControl miceObesity modelRisk factorsMyocardial diseaseDysfunction
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 hypertrophyFrequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration
Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM. Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nature Genetics 2017, 49: 1346-1353. PMID: 28783163, PMCID: PMC5736145, DOI: 10.1038/ng.3929.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedCells, CulturedDiploidyGene Expression ProfilingHeartImmunoblottingIn Situ Hybridization, FluorescenceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, ConfocalMyocardiumMyocytes, CardiacProtein KinasesProtein Serine-Threonine KinasesRegenerationZebrafish
2016
Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy
Zhou J, Ahmad F, Parikh S, Hoffman NE, Rajan S, Verma VK, Song J, Yuan A, Shanmughapriya S, Guo Y, Gao E, Koch W, Woodgett JR, Madesh M, Kishore R, Lal H, Force T. Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy. Circulation Research 2016, 118: 1208-1222. PMID: 26976650, PMCID: PMC4843504, DOI: 10.1161/circresaha.116.308544.Peer-Reviewed Original ResearchConceptsAdult cardiac myocytesCardiac myocytesCardiac homeostasisGSK-3βSerial echocardiographic analysisCardiac myocyte-specific deletionGSK-3Normal cardiac homeostasisMitotic catastropheCell cycle dysregulationDouble knockout heartsVentricular dysfunctionOverall survivalTamoxifen treatmentCardiac protectionMyocardial infarctionEchocardiographic analysisHeart functionGlycogen synthase kinaseIsolated adult cardiac myocytesSynergistic protectionGSK-3 isoformsCell cycle activityMarked activationCell cycle progression
2014
Troponin I-Interacting Protein Kinase
Lal H, Ahmad F, Parikh S, Force T. Troponin I-Interacting Protein Kinase. Circulation Journal 2014, 78: 1514. PMID: 24899531, PMCID: PMC4151348, DOI: 10.1253/circj.cj-14-0543.Peer-Reviewed Original ResearchConceptsIR injuryMyocardial infarctionCardiomyocyte deathNew drug targetsNovel genetic animal modelsEffective myocardial reperfusionAcute coronary syndromeIschemia-reperfusion injuryPercutaneous coronary interventionCoronary artery diseaseCause of deathProfound oxidative stressPromising new drug targetGenetic animal modelsCardiac troponin ITNNI3KDrug targetsCoronary syndromeCoronary interventionArtery diseaseMyocardial reperfusionReperfusion injuryCardiac dysfunctionIschemic injuryInfarct size