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 clamp
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