Stuart Campbell
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About
Research
Publications
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 Original ResearchContractile phenotypes of engineered heart tissues derived from hypertrophic cardiomyopathy patients lacking sarcomeric mutations
Rasheed Y, Young S, Halder S, Li X, Stendahl J, Campbell S. Contractile phenotypes of engineered heart tissues derived from hypertrophic cardiomyopathy patients lacking sarcomeric mutations. Biophysical Journal 2024, 123: 388a. DOI: 10.1016/j.bpj.2023.11.2357.Peer-Reviewed Original ResearchDifferent mechanistic and molecular cues modulate divergent phenotypes in HCM and DCM mutations to TPM1
Halder S, Rynkiewicz M, Moore J, Lehman W, Campbell S. Different mechanistic and molecular cues modulate divergent phenotypes in HCM and DCM mutations to TPM1. Biophysical Journal 2024, 123: 18a. DOI: 10.1016/j.bpj.2023.11.222.Peer-Reviewed Original ResearchTTN 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 samplesClassifying 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
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 ResearchIncreased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy
Rupert C, López J, Cortez-Toledo E, De la Cruz Cabrera O, Chesler N, Simpson P, Campbell S, Baker A. Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy. AJP Heart And Circulatory Physiology 2023, 324: h293-h304. PMID: 36637971, PMCID: PMC9886349, DOI: 10.1152/ajpheart.00279.2022.Peer-Reviewed Original ResearchConceptsHuman heart failureHeart failureAR stimulationChronic stimulationLength-dependent activationVehicle treatmentHeart tissueAdrenergic receptorsHuman EHTsAnimal heart failure modelNovel heart failure therapiesHeart failure therapyHeart failure modelMultiple preclinical modelsFailure therapyAgonist treatmentSeparate control experimentsPreclinical modelsDrug washoutTherapeutic effectTranslational significanceHuman myocardiumBaseline testingRNA-seq analysisPig myocardium
News
News
- March 11, 2024
Engineering a Heart Conduit: New $2M NIH Grant for Yale Research
- April 18, 2023
Akar and Campbell Awarded R01 to study mechanisms and develop therapies for arrhythmogenic cardiomyopathies
- July 27, 2022
Uncovering New Approaches to a Common Inherited Heart Disorder
- June 01, 2021
Student Research Day Celebrates Students and Mentors