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Epigenetic check-point regulates polarization of monocytes post-MI
Myocardial infarction (MI) triggers a wound healing response that involves rapid recruitment of immune cells, notably myeloid cells, to the heart. This innate immune response is required for efficient healing, and alteration of its kinetics may contribute to poor infarct remodeling driving heart failure development. In the latest issue of Nature Communications, the team led by Dr. Fraineau described for the first time the role of an epigenetic switch in regulating the kinetics and profiles of the innate immune response post-MI. Specifically, they uncovered that an epigenetic transcriptional repressive enzyme, named EZH2, serves as an epigenetic check-point during polarization of monocytes toward an immunomodulatory pro-regenerative macrophage phenotype. Using an epigenetic pharmacological inhibitor of EZH2, this check-point can be suppressed, thus enhancing the transcriptomic program resulting in generation of more immunomodulatory macrophages. This led to an acceleration of the innate immune response after MI, resulting in reduced deleterious infarct scar remodeling, and prevention of post-MI aggravation of cardiac dysfunction. Altogether, Fraineau et al. identified an original epigenetic mechanism governing macrophage polarization toward either proinflammatory or immunomodulatory phenotypes, thus revealing epigenetic mechanisms as a novel therapeutic target to improve inflammatory kinetics post-MI to prevent heart failure development.
See further: open access article or video presentation by Dr Fraineau
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Winning-Normandy: PROTECT
The MSCA Winning-Normandy project PROTECT: "Pharmacological tReatment Of acuTe dECompensaTed heart failure: focus on metabolic remodeling" was initiated in 2022 in our laboratory. This project, led by Postdoctoral researcher Francesca Lockwood together with Pr Paul Mulder, will investigate the molecular, and notably metabolic, changes that occur during Acute Decompensated Heart Failure (ADHF). This project is developed in parallel to a recent ANR project (2019-2022) focused on ADHF: RESIST-HF.
Biography:
Francesca Lockwood has multidisciplinary experience in areas including cancer and cardiovascular pathophysiology and pharmacology from both academia and the biotech sector.
Francesca Lockwood undertook a Pharmacology degree with honours (awarded in 2016) from the University of Portsmouth (United Kingdom) and during this programme she obtained an Erasmus placement where she worked at Inserm U1096 (Rouen) , in 2015, investigating ‘Cardiovascular effects of the IL-1β Antibody Gevokizumab’, which she used for her bachelor thesis.
Alongside completing the final year of her bachelors, Francesca researched at the Institute of Biomedical & Biomolecular Science at the University of Portsmouth on ‘The effects of stress on the locus coeruleus and its contribution to Parkinson’s disease’. The data generated contributed to a successful funding application ‘The Role of the Brain Locus Coeruleus Nucleus in Parkinson’s Disease-induced stress and anxiety’ to the project supervisor Dr Jermone Swinny of £224,978 from Parkinson’s UK, awarded in 2016. Francesca then explored ‘Chemoresistance in glioblastoma multiforme through REDOX adaptations’ during her Masters of Research degree at the Brain Tumour institute at the University of Portsmouth which entailed full time research while completing the degree (awarded in 2017).
Francesca then moved into the biotech industry at Primer Design, Southampton, UK which involved technical sales/advice, team management and business strategy guidance. During this position Francesca obtained a Research assistant and Doctoral Research fellow position at Ulleval Hospital - University of Oslo, Norway, to investigate ‘Mechanisms of cardiac fibrosis from cardiac hemodynamic overload’. While in this position, Francesca was headhunted by a global private biotech company, developing cancer vaccines in an industrial scientist position, and was quickly promoted to project leader. After around 5 months at this company Francesca was offered the position of CEO of the US daughter company.
During this time Francesca’s application for the Winning Normandy grant with Inserm U1096 was successful and she chose this position instead of CEO and started in October 2022. In this position Francesca will be investigating the ‘Metabolic mechanisms during cardiac remodelling in order to explore therapeutics targets and to investigate the efficacy of potential therapeutics on these pathways’.
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L'Alliance du cœur en 2023
L'alliance du coeur fete ses 30 ans cette été, et le Journées du coeur fete ses 10 ans. Voir le programme proposé: https://online.fliphtml5.com/ervmz/nvyw/#p=1
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Inserm U1096 - Laboratory EnVI
Research performed in Inserm U1096 Unit in Rouen, concerns evaluation of the mechanisms behind and novel treatments of cardiovascular diseases, focusing on vascular protection and improvement of cardiac contractile function. This research is transversal, and performed both in experimental models and in human.