2024
Classifying pathogenicity of TPM1 variants of unknown significance using in vitro and in silico approaches
Campbell S, Creso J, Firlar I, Halder S, Lehman W, Rynkiewicz M, Moore J. Classifying pathogenicity of TPM1 variants of unknown significance using in vitro and in silico approaches. Journal Of Cardiac Failure 2024, 30: s3. DOI: 10.1016/j.cardfail.2023.11.005.Peer-Reviewed Original ResearchHypertrophic cardiomyopathyUnknown significanceContractile forceOngoing clinical challengeFirst-degree relativesGenetic testing yieldSlowing of relaxationViral exposureContractile weaknessClinical challengeHypercontractile phenotypeHCM mutationsMyofilament activityHeart tissueMild phenotypeFurther studiesContractile behaviorSignificant increaseHEHTTesting yieldDCM mutationsMinimal effectVUSPathogenicityPhenotype
2022
Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxation