Postdoctoral Scientist (M/F) in Cardiac Physiopathology

Environment

The Laboratory of Signalling and Cardiovascular Pathophysiology (UMR-S 1180) is a joint INSERM and University Paris-Saclay funded research unit. It is part of the Faculty of Pharmacy of the University Paris-Saclay, located since 2022 in a brand-new building in Orsay, right in the middle of the Paris-Saclay Cluster. The general goal of the unit is to better understand the molecular and cellular mechanisms by which physiological and pathological stimuli act on cardiac function. The characterization of the underlining signalling cascades is necessary for the identification of new therapeutic targets to treat heart failure (HF). The postdoctoral scientist will integrate the team 2 of the unit. The research of this team is focused on cyclic nucleotides (CNs) signalling which act as second messengers for sympathetic and parasympathetic systems, nitric oxide (NO) and natriuretic peptides (NPs). The dysregulation of these neurohormonal systems plays a fundamental role in the progression of HF and are currently major targets of treatments for this syndrome.

Scientific project

The project, funded by the French National Research Agency (ANR PDEtreat4heart), is to test whether increased cardiac phosphodiesterases (PDEs) activity could limit progression toward maladaptive hypertrophy and associated arrhythmias. To fulfil this goal, gene therapy with AAV-9 encoding for PDE3A in mouse models of HF will be performed and its benefits compared to that of actual treatments.

We have shown recently that cardiac gene therapy with specific isoforms of these enzymes PDE4B or PDE2A is protective in preclinical models of HF.(1,2) While PDE2 and PDE4 are expressed in the human heart, PDE3A is the major PDE controlling excitation-contraction coupling in the human heart and is the target of the cardiotonic drug milrinone. Milrinone improves systolic function in acute HF but its chronic use in patients with HErEF increases mortality, probably by favouring cardiac arrhythmias. Several studies including ours, showed that PDE3A is decreased in pathological conditions.(3) We believe that this promotes cardiac arrhythmias. In addition, PDE3A has been proposed as a negative regulator of apoptosis and hypertrophy(3) further supporting our hypothesis that increasing PDE3A activity would be beneficial to treat HF.

The budget finances a full-time scientist position at UMR-S 1180 for one year, starting as soon as possible in 2025. A potential prolongation will depend on securing additional funds.

1. Karam et al., 2020 Circulation ; 142(2):161-174. doi:10.1161/CIRCULATIONAHA.119.042573.

2. Kamel et al., 2024 JAHA ; in revision (BioRxvid doi: https://doi.org/10.1101/2023.04.17.537274)

3. Kamel et al., 2023 Nat. Rev. Cardiol.; 20(2): 90-108. doi: 10.1038/s41569-022-00756-z.

Qualifications

Applicants should have a PhD and (ideally) a few years of postdoctoral experience. A background in cardiac pathophysiology, animal models of heart failure are required. Experience in optical mapping and imaging (FRET and Ca²⁺ imaging) will be valued. Independence and strong motivation are essential. The job will require skills in physiology, imaging, protein expression/purification, biochemical assays, etc., as well as data analysis and science communication. Fluency in English is required.

Our offer

We offer the special opportunity to contribute to an exciting scientific project. The postdoc will benefit from all laboratory expertise as well as from a large number of core facilities. Our worldwide collaborative network is substantial and offers many opportunities for professional development. The salary will depend on qualifications and professional experience and is calculated in accordance with INSERM salary scales.