In a new study, entitled "CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury" published in J Adv Res in Jan 2023, Dr Leullier et al investigate the physiological role of the N-terminal phosphatase activity (sEH-P) of the enzyme soluble epoxide hydrolase (sEH).  CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity. Thus study, lead by Pr Jeremy Bellien, reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.

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’.

Dr Ebba Brakenhielm is Coordinator on a recently intitiated ANR international collaborative project entitled CITE-LYMPH : «Ciblage lymphatique cardiaque des cellules immunitaires» selected in the ANR PRCI 2022 axis «Collaboration bilatérale ANR/ DFG»

This project is developed together with Pr Alma Zernecke-Madsen (Institut für Experimentelle Biomedizin der Universität Würzburg, Germany).

 Pr Jeremy Bellien is Coordinator on a recently intitiated ANR international collaborative project entitled PHASM : «L'activité phosphatase de l'époxyde hydrolase soluble comme nouvelle cible dans les maladies cardiométaboliques» selected in the ANR PRCI 2022 axis «Collaboration bilatérale ANR/ DFG»

This project is developed together with  Pr Ewgeinj Proschak (Heisenberg-Professor for Drug Design at the Institut für Pharmazeutische Chemie, Goethe-Universität Frankfurt am Main, Germany).