Stuart Campbell
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2025
Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models
Halder S, Bellitto J, Rynkiewicz M, Cheung F, Liu D, Firlar I, Bongiorno A, Barry M, Sewanan L, Moore J, Lehman W, Campbell S. Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models. The Journal Of Precision Medicine Health And Disease 2025, 2: 100008. DOI: 10.1016/j.premed.2025.100008.Peer-Reviewed Original ResearchIn vitro motilityFilament motilityContext of cardiomyopathyVariant classificationGenetic screeningTwitch contraction forceComputational pipelineMyosin activityEvaluate pathogenicityDiversity changesFunctional studiesIn silicoTropomyosinTPM1VUSMotilityInherited cardiomyopathyCa2+ sensitivityVariantsIn vitro modelIn vitro dataReduced abilityIPSC-derived cardiomyocytesLow Ca2+Ca2+Advanced tissue-engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes
Luo H, Anderson C, Li X, Lu Y, Hoareau M, Xing Q, Fooladi S, Liu Y, Xu Z, Park J, Fallon M, Thomas J, Gruber P, Elder R, Mak M, Riaz M, Campbell S, Qyang Y. Advanced tissue-engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes. Acta Biomaterialia 2025, 211: 92-103. PMID: 40582540, PMCID: PMC12338880, DOI: 10.1016/j.actbio.2025.06.055.Peer-Reviewed Original ResearchSingle ventricle congenital heart defectsHuman induced pluripotent stem cell-derived cardiomyocytesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesCell-derived cardiomyocytesCongenital heart defectsHuman umbilical arteryUmbilical arteryHeart defectsPulmonary circulationDecellularized human umbilical arteriesHeart tissueLife-threatening defectsLife-threatening disorderLong-term complicationsEngineered Heart TissueFontan surgeryFunctioning ventriclePrompt treatmentHeart failureSpontaneous beatingPump functionImprove outcomesPressure generationConventional treatmentApplication of instant assembly of collagen to bioprint cardiac tissues
Xiao H, Liang Z, Gong X, Jordan S, Rossello-Martinez A, Gokhan I, Li X, Wen Z, Lee S, Campbell S, Qyang Y, Mak M. Application of instant assembly of collagen to bioprint cardiac tissues. APL Bioengineering 2025, 9: 026124. PMID: 40520649, PMCID: PMC12165719, DOI: 10.1063/5.0252746.Peer-Reviewed Original ResearchTissue engineeringFabrication of biomimetic tissuesCardiac tissue engineeringSupport bathCollagen bioinkBioprinting techniquesBiomimetic tissuesBioprinting methodsEngineered tissuesFabrication techniquesImmediate gelationBioprintingComplex tissue geometriesPolydimethylsiloxaneStructural fidelityNutrient diffusionFabricationTissue geometryEngineeringDamaged heart tissueBioinkStructural supportCardiac modelsCardiac tissueTissue maturationScreening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants
Wen J, Campbell S, Moore J, Lehman W, Rynkiewicz M. Screening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants. Journal Of Molecular And Cellular Cardiology 2025, 203: 82-90. PMID: 40268117, PMCID: PMC12135046, DOI: 10.1016/j.yjmcc.2025.04.009.Peer-Reviewed Original ResearchConceptsDeleterious effects of mutationsTropomyosin-actin interactionsSingle nucleotide mutationsEffects of mutationsThin filament regulationDilated CardiomyopathyTropomyosin sequencesActin interactionNucleotide mutationsFilament regulationMutation-sensitiveSubcellular unitsMutantsPathological cardiac remodelingTropomyosinActinThin filamentsEarly therapeutic interventionFunctional analysisMutationsInherited cardiomyopathyCardiac remodelingCardiac functionRegulatory BCardiomyopathy
2024
Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy associated TPM1 variants
Halder S, Rynkiewicz M, Kim L, Barry M, Zied A, Sewanan L, Kirk J, Moore J, Lehman W, Campbell S. Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy associated TPM1 variants. Journal Of Clinical Investigation 2024, 134: e179135. PMID: 39436707, PMCID: PMC11645150, DOI: 10.1172/jci179135.Peer-Reviewed Original ResearchTPM1 mutationActin thin filamentsDilated CardiomyopathyE54KPhenotypic diversityMyosin activityStem cell-derived cardiomyocytesGene expressionHuman engineered heart tissueIncreased calcium sensitivitySarcomeric proteinsCell-derived cardiomyocytesThin filamentsK mutationMolecular eventsTPM1MutationsClinical phenotypePhenotypeAllosteric interactionsGenesMuscle contractilityCalcium sensitivityInherited disorderAssociation rateIn silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R
Creso J, Gokhan I, Rynkiewicz M, Lehman W, Moore J, Campbell S. In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R. Frontiers In Physiology 2024, 15: 1452509. PMID: 39282088, PMCID: PMC11392859, DOI: 10.3389/fphys.2024.1452509.Peer-Reviewed Original ResearchDilated CardiomyopathyManifestation of dilated cardiomyopathyTropomyosin-actin interactionsIntact cardiac muscleIsometric twitch forceCardiac muscle disordersSevere heart failureHuman engineered heart tissueGenotype-phenotype relationshipsDose-dependent mannerDuration of contractionIn silico predictionIn vitro modelDepressed contractilityMutant tissueCardiac sarcomereLinkage studiesHeart failureTropomyosin chainTwitch contractionsCardiac thin filamentsInherited disorderMuscle disordersMutation pathogenicityCardiac muscleEngineered 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 Reviews, Practice Guidelines, Standards, and Consensus StatementsTTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance
Hinson J, Campbell S. TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance. Journal Of Clinical Investigation 2024, 134: e175206. PMID: 38226618, PMCID: PMC10786689, DOI: 10.1172/jci175206.Peer-Reviewed Original ResearchConceptsTruncating variantsSubcellular localizationTitin truncating variantsComplex proteinsSarcomere integrityGenetic lesionsTitin proteinDilated CardiomyopathyFunctional consequencesProteinVariable penetranceSarcomeric dysfunctionImpaired cardiac contractilityTitinSarcomeric structural integrityAlternative therapeutic approachCardiac contractilityVariantsPotential mechanismsTherapeutic approachesHaploinsufficiencyDCM samples
2023
Rational engineering of lung alveolar epithelium
Leiby K, Yuan Y, Ng R, Raredon M, Adams T, Baevova P, Greaney A, Hirschi K, Campbell S, Kaminski N, Herzog E, Niklason L. Rational engineering of lung alveolar epithelium. Npj Regenerative Medicine 2023, 8: 22. PMID: 37117221, PMCID: PMC10147714, DOI: 10.1038/s41536-023-00295-2.Peer-Reviewed Original ResearchMechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L
Halder S, Rynkiewicz M, Creso J, Sewanan L, Howland L, Moore J, Lehman W, Campbell S. Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L. PNAS Nexus 2023, 2: pgad011. PMID: 36896133, PMCID: PMC9991458, DOI: 10.1093/pnasnexus/pgad011.Peer-Reviewed Original Research
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Yale Only Dillon Chen, MD, PhD - Stuart Campbell