{
  "abstract": "The adult mammalian heart has a limited ability to regenerate lost myocardium following myocardial infarction (MI), largely due to the poor proliferative capacity of cardiomyocytes (CMs). Dual-specificity tyrosine phosphorylation–regulated kinase 1A (DYRK1A) is a known regulator of cell quiescence, though the mechanisms underlying its function remain unclear. Previous studies have shown that pharmacological inhibition of DYRK1A using harmine induces CM cell cycle reentry after ischemia/reperfusion (I/R) MI. Here, we developed a computational network model of DYRK1A-mediated regulation of the cell cycle, which predicts how DYRK1A inhibition promotes CM reentry. To validate these predictions, we tested selective DYRK1A inhibitors and observed robust induction of cell cycle activity in neonatal rat cardiomyocytes (NRCMs). Integrating our network model with bulk RNA sequencing data from DYRK1A inhibitor–treated NRCMs, we identified E2F1 as a key transcriptional driver of cell cycle gene expression. Finally, we demonstrate that both pharmacological and post-developmental inhibition of DYRK1A enhances heart function and increases CM cycling following I/R MI. Our findings suggest that functional recovery induced by small-molecule inhibitors of DYRK1A is mediated by the induction of cycling CMs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology",
    "Department of Medicine",
    "Department of Biomedical Engineering, and",
    "Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.",
    "Perha Pharmaceuticals, Roscoff, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bryce C. Murillo"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexander Young"
    },
    {
      "affs": [
        2
      ],
      "name": "Kaitlyn L. Wintruba"
    },
    {
      "affs": [
        3
      ],
      "name": "Alexander J. Eichert"
    },
    {
      "affs": [
        1
      ],
      "name": "Klara Siejda"
    },
    {
      "affs": [
        1
      ],
      "name": "Dennon Hoernig"
    },
    {
      "affs": [
        1
      ],
      "name": "Leigh A. Bradley"
    },
    {
      "affs": [
        2
      ],
      "name": "Bryana N. Harris"
    },
    {
      "affs": [
        2
      ],
      "name": "Catherine Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Michelle Wu"
    },
    {
      "affs": [
        4
      ],
      "name": "Emmanuel Deau"
    },
    {
      "affs": [
        4
      ],
      "name": "Mattias F. Lindberg"
    },
    {
      "affs": [
        4
      ],
      "name": "Laurent Meijer"
    },
    {
      "affs": [
        2
      ],
      "name": "Jeffrey J. Saucerman"
    },
    {
      "affs": [
        1
      ],
      "name": "Matthew J. Wolf"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8sfefwefbkxg5.bib",
  "cited_by": 3,
  "doi": "10.1172/jci.insight.200429",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726558/",
  "id": "8sfefwefbkxg5",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.200429",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Congenital heart defects research"
    ]
  ],
  "openalex": "W7213471924",
  "pdf_url": "http://insight.jci.org/articles/view/200429/files/pdf",
  "pmcid": "PMC13726558",
  "pmid": "42752366",
  "published": "2026-09-17",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/8sfefwefbkxg5.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:52Z",
      "native_id": "PMC13726558",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci.insight.200429"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Congenital heart defects research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Network modeling predicts how DYRK1A inhibition promotes cardiomyocyte cycling after ischemia/reperfusion injury",
  "title_text": "Network modeling predicts how DYRK1A inhibition promotes cardiomyocyte cycling after ischemia/reperfusion injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:28Z",
  "url": "https://research.draconitic.com/paper/8sfefwefbkxg5",
  "venue": "JCI Insight",
  "versions": []
}