Benjamin Keepers, MD, PhD
Hospital ResidentAbout
Research
Publications
2024
Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression
Huang P, Xu J, Keepers B, Xie Y, Near D, Xu Y, Hua J, Spurlock B, Ricketts S, Liu J, Wang L, Qian L. Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression. Molecular Therapy - Nucleic Acids 2024, 35: 102390. PMID: 39720701, PMCID: PMC11666955, DOI: 10.1016/j.omtn.2024.102390.Peer-Reviewed Original ResearchActivity of endogenous factorsDirect cardiac reprogrammingInduced cardiomyocytesCardiac reprogrammingExpression of cardiac transcription factorsCardiac transcription factorsTranscription factorsReprogramming of fibroblastsSingle-guide RNAViral toxicityViral vectorsExogenous transcription factorsImmune responseEpigenetic barriersGATA4 activityRegenerative purposesClinical applicationEndogenous factorsEndogenous transcription factorsGenomic mutationsExogenous expressionReprogrammingFibroblastsEndogenous gene expressionHuman fibroblastsDirect conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg
Farber G, Dong Y, Wang Q, Rathod M, Wang H, Dixit M, Keepers B, Xie Y, Butz K, Polacheck W, Liu J, Qian L. Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg. Nature Communications 2024, 15: 4170. PMID: 38755186, PMCID: PMC11098819, DOI: 10.1038/s41467-024-48354-6.Peer-Reviewed Original ResearchConceptsCardiac fibroblastsEndothelial cellsEndothelial-like cellsIn vivoRepair injured tissuesFunction in vitroInduced endothelial cellsConversion of cardiac fibroblastsInfarct siteReprogramming strategiesMyocardial infarction siteReprogramming approachInjured tissueInjury resultsVascular perfusionEndothelial-likeScar regionPhysiological function in vitroIn vitroOrgan-specificFibroblastsHeterogeneous populationCellsReprogramming
2023
On Your MARCKS…Get Set…Go The Race to Explore Myristoylation in HF Is Underway ∗
Keepers B, Jensen B. On Your MARCKS…Get Set…Go The Race to Explore Myristoylation in HF Is Underway ∗. JACC Basic To Translational Science 2023, 8: 1283-1284. PMID: 38094683, PMCID: PMC10714165, DOI: 10.1016/j.jacbts.2023.08.007.Peer-Reviewed Original ResearchTranslational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition
Xie Y, Wang Q, Yang Y, Near D, Wang H, Colon M, Nguyen C, Slattery C, Keepers B, Farber G, Wang T, Lee S, Ian Shih Y, Liu J, Qian L. Translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition. Nature Cardiovascular Research 2023, 2: 1060-1077. PMID: 38524149, PMCID: PMC10959502, DOI: 10.1038/s44161-023-00344-5.Peer-Reviewed Original ResearchTranslational regulationTranslational landscapeLayer of regulatory mechanismLoss-of-function screensY-box binding protein 1ICM reprogrammingBinding protein 1Induced cardiomyocytes generationFate acquisitionInduced cardiomyocytesEpigenetic mechanismsTranscriptome profilingTranslational levelY-boxRegulatory mechanismsYBX1Reprogramming of fibroblastsReprogrammingDirect reprogramming of fibroblastsCardiac reprogrammingProtein 1Mouse model of myocardial infarctionReduced scar sizeDirect reprogrammingModel of myocardial infarctionOptimized protocol for direct cardiac reprogramming in mice using Ascl1 and Mef2c
Wang H, Keepers B, Liu J, Qian L. Optimized protocol for direct cardiac reprogramming in mice using Ascl1 and Mef2c. STAR Protocols 2023, 4: 102204. PMID: 36989109, PMCID: PMC10074248, DOI: 10.1016/j.xpro.2023.102204.Peer-Reviewed Original ResearchCardiac reprogrammingNeonatal mouse cardiac fibroblastsIntermediate progenitor stageDirect cardiac reprogrammingCardiomyocyte-like cellsMouse cardiac fibroblastsConversion of fibroblastsCalcium fluxReprogramming factorsProgenitor stageCardiac fibroblastsSarcomere structureAscl1MEF2CReprogrammingMiceGene expressionFibroblastsOptimized protocol
2022
Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes
Wang H, Keepers B, Qian Y, Xie Y, Colon M, Liu J, Qian L. Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes. Cell Stem Cell 2022, 29: 1491-1504.e9. PMID: 36206732, PMCID: PMC9557912, DOI: 10.1016/j.stem.2022.09.006.Peer-Reviewed Original ResearchConceptsTranscription factorsLineage-specific featuresRegulatory transcription factorsAltering cell fateChIP-seqRNA-seqEpigenome remodelingCell fateTranscriptional activityASCL1 bindingNeuronal genesStem cell biologyReprogramming cellsCell biologyReprogrammingAscl1Cardiac genesField of stem cell biologyTranscriptionGenesDirect reprogrammingMEF2CReprogramming approachCardiomyocyte phenotypeCardiac reprogramming
2020
An Optimized Protocol for Human Direct Cardiac Reprogramming
Garbutt T, Zhou Y, Keepers B, Liu J, Qian L. An Optimized Protocol for Human Direct Cardiac Reprogramming. STAR Protocols 2020, 1: 100010. PMID: 32728671, PMCID: PMC7390466, DOI: 10.1016/j.xpro.2019.100010.Peer-Reviewed Original Research
2019
Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming
Zhou Y, Liu Z, Welch J, Gao X, Wang L, Garbutt T, Keepers B, Ma H, Prins J, Shen W, Liu J, Qian L. Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming. Cell Stem Cell 2019, 25: 149-164.e9. PMID: 31230860, PMCID: PMC6684137, DOI: 10.1016/j.stem.2019.05.020.Peer-Reviewed Original ResearchConceptsCell fate transitionsCell fate determinationSingle-cell transcriptomic studiesCell fate conversionFate transitionsSingle-cell transcriptome analysisReprogramming progressionFate determinationDNA methylationFunctional screeningFate conversionCellular reprogrammingDownstream targetsAnalysis pipelineAnalytical pipelineFibroblast stateReprogrammingCell plasticityReprogramming factorsMolecular featuresCellsHuman cardiacTrajectory prediction algorithmPrediction algorithmFibroblastsWhat's in a cardiomyocyte – And how do we make one through reprogramming?
Keepers B, Liu J, Qian L. What's in a cardiomyocyte – And how do we make one through reprogramming? Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research 2019, 1867: 118464. PMID: 30922868, PMCID: PMC6911029, DOI: 10.1016/j.bbamcr.2019.03.011.Peer-Reviewed Original Research
2018
Tension-dependent regulation of mammalian Hippo signaling through LIMD1
Ibar C, Kirichenko E, Keepers B, Enners E, Fleisch K, Irvine K. Tension-dependent regulation of mammalian Hippo signaling through LIMD1. Journal Of Cell Science 2018, 131: jcs214700. PMID: 29440237, PMCID: PMC5897721, DOI: 10.1242/jcs.214700.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdherens JunctionsAnimalsCarrier ProteinsCell CountCell ProliferationCo-Repressor ProteinsCytoskeletal ProteinsCytoskeletonDogsHEK293 CellsHippo Signaling PathwayHumansIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsMechanotransduction, CellularPhosphoproteinsProtein Serine-Threonine Kinasesrho-Associated KinasesSignal TransductionTranscription FactorsTumor Suppressor ProteinsYAP-Signaling ProteinsConceptsMammalian Hippo signalingHippo signalingLATS kinasesFamily proteinsRegulation of Lats kinasesLocalization to adherens junctionsRegulation of Hippo signalingJunctional localizationDensity-dependent regulationRho-mediatedRho activationAdherens junctionsAjubaLIMD1Biomechanical cuesKinaseJunctional complexesRhoCell densityProteinPathwayRegulationWTIPCytoskeletonSignal
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