# Computational and Experimental Modeling of Cardiomyocyte Proliferation

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $709,107

## Abstract

Summary
Heart failure arises in large part due to the very limited ability of cardiomyocytes to regenerate following injury.
Recent studies have identified some molecular regulators of cardiomyocyte proliferation in mammals, but the
field lacks an understanding of how these and yet-to-be identified components work as a system to regulate
cardiomyocyte proliferation. A better understanding of the pathways that control CM proliferation and cell cycle
exit is needed in order to develop strategies that stimulate CM proliferation as a regenerative therapy. Here, we
integrate innovative computational and experimental methods to develop a systems-level understanding of
cardiomyocyte proliferation. First, we develop a literature-based computational model of the molecular network,
comprising known regulators of cardiomyocyte proliferation. This network model is expanded mechanistically
to include novel regulators of cardiomyocyte proliferation that we have discovered through a genome-wide
phenotypic screen, including several in a TGF-beta module. Model-predicted regulators within this TGF-beta
module are validated experimentally in mouse cardiomyocytes, human induced pluripotent stem-cell derived
cardiomyocytes, and an in vivo mouse model of cardiac regeneration. Overall, this study will provide novel
candidate therapeutic targets for cardiomyocyte proliferation, the first mechanistic model integrating these
candidates and known regulators of cardiomyocyte proliferation, and experimental validation that the model
can predict network perturbations that enhance cardiomyocyte proliferation in vitro and in vivo.

## Key facts

- **NIH application ID:** 10337761
- **Project number:** 1R01HL160665-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jeffrey J. Saucerman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $709,107
- **Award type:** 1
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337761

## Citation

> US National Institutes of Health, RePORTER application 10337761, Computational and Experimental Modeling of Cardiomyocyte Proliferation (1R01HL160665-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10337761. Licensed CC0.

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