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4D Heart-on-a-chip: Modeling circadian rhythms in the human heart to study cardiac (patho)physiology and advance therapy

Objective

Cardiovascular disease is the leading cause of death worldwide. Growing evidence shows that circadian rhythms profoundly shape cardiac health, governing the timing and severity of cardiac events, influencing drug efficacy, and, when chronically disrupted (e.g. in shift work, sleep disorders, or jet lag), markedly increasing disease risk. Yet, the mechanisms by which they regulate the human heart remain unknown, as current knowledge relies largely on animal models with limited translational relevance. Predictive human heart models capable of capturing circadian rhythms and their regulation would be transformative for cardiac research and precision medicine. Building on my expertise in engineered cardiac tissues and organs-on-chip (OOC), I propose to develop a pioneering 4D heart-on-a-chip that models, monitors, and manipulates circadian rhythms, in a physiologically relevant model of the human heart (Aim 1). This platform will integrate tissues composed of reporter cell lines for real-time tracking of intrinsic circadian rhythmicity in tissues linked to an OOC system delivering oscillating hormones and metabolites that simulate light-dark and feeding-fasting cycles. These cues will be applied through an automated feedback-loop system, either in synchrony or in deliberate misalignment with the tissue’s intrinsic rhythms, to enable modeling of both homeostatic and disrupted conditions. Using this unique approach, I propose to address two fundamental questions at the intersection of cardiac biology and chronobiology: (i) how the time-of-day modulates cardiac sensitivity to injury (Aim 2), and (ii) how circadian misalignment leads to cardiac disease (Aim 3). Beyond mechanistic studies, the 4D platform will provide an unprecedented testbed for developing circadian-guided therapies. Successful completion of this work will help reduce the global burden of heart disease and transform the prediction, prevention, and treatment of time-sensitive cardiovascular pathologies.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2026-STG

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Host institution

TEL AVIV UNIVERSITY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 880 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 880 000,00

Beneficiaries (1)