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Decoding Monocyte Metabolism in Myocardial Infarction: A Time-Sensitive Approach to Limiting Heart Failure

Project description

Reprogramming immune cells to heal the heart

After a heart attack, the immune system plays a vital role in recovery by clearing damaged tissue and beginning the repair process. However, if inflammation lasts too long or is not properly regulated, it can cause damage. With the support of the Marie Skłodowska-Curie Actions programme, the 3MI project will investigate how the metabolism of key immune cells such as monocytes shapes their role in healing or damaging cardiac tissue. To identify pathways that control inflammation, researchers will track metabolic changes over time. The rationale is to modulate monocyte metabolism for improved heart repair and new treatments for cardiovascular diseases.

Objective

Cardiovascular diseases (CVD), particularly myocardial infarction (MI), are partly driven by chronic inflammation, in which myeloid cells, such as monocytes and macrophages, play a central role. This project aims to elucidate the metabolic mechanisms regulating monocyte function and their impact on post-MI recovery. Emerging evidence suggests that the metabolic state of myeloid progenitor cells and their descendants critically influences their pro- or anti-inflammatory functions. While glycolysis dominates early after MI, fatty acid oxidation takes over later stages, indicating that metabolic reprogramming is essential for monocyte and macrophage function.

In this project, we will investigate the metabolic signatures of monocytes at different time points post-MI using a preclinical mouse model and the human HIBISCUS STEMI cohort. We aim to identify key metabolic pathways that can be targeted to modulate inflammation by employing single-cell RNA sequencing and single-cell metabolic assays. In mouse models, we will further test the effects of transiently inhibiting glycolysis or fatty acid oxidation in monocytes, using genetically modified mice, to determine whether this approach improves cardiac function and limits heart failure.

Additionally, the fellowship will provide essential soft skills training in project management, mentoring, and grant writing, which are crucial for my transition to an independent research position. These skills will enhance my leadership abilities and prepare me for future academic and industrial opportunities.
This research will provide new insights into the role of metabolism in myelopoiesis and inflammation and could lead to novel therapeutic strategies to improve outcomes in CVD patients.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

HOSPICES CIVILS DE LYON
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.

€ 242 260,56
Address
QUAI DES CELESTINS 3
69002 Lyon
France

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Region
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
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