Postdoc position in vascular endothelium function and targeted therapy

The Institute of Metabolic and Cardiovascular Diseases (I2MC) is recognized for its translational research in the field of metabolic (obesity, diabetes, dyslipidemias) and cardiovascular (thrombosis, atherosclerosis, cardiac and renal failure) diseases.

The I2MC teams share a similar "research philosophy" consisting in multidisciplinary approaches from basic science to clinical trials. In terms of basic research, the laboratories have a large expertise in membrane and intracellular receptors, cell signaling, metabolic pathways, cell/cell interactions and the mechanisms of tissue remodeling. To establish the pathophysiological relevance of the results obtained in basic research, I2MC teams have created original animal models and phenotyping techniques that have gained national recognition and are one of the highlights of the Institute. Translation to the clinic is greatly facilitated by the location within the Rangueil site of Toulouse University Hospitals. Notably, clinical departments devoted to nutrition, cardiovascular and renal diseases, obesity and diabetes are in close vicinity of I2MC.

The industrial valorization of the research is another strength of I2MC. Numerous structured collaborations are ongoing with industrial partners, from SMEs to big pharmas. I2MC research directly contributed to the creation of 4 start-up companies.

I2MC offers scientists a diverse set of competence through its 7 core facilities (Lipidomics, Imaging, Bioinformatics, Functional Biochemistry, Cytometry, Histology, Genomics & Transcriptomics). These Facilities are central to the scientific development of I2MC and a major asset in terms of recognition.

Endothelial cells, which line the surface of blood vessels to form the endothelium, largely contribute to the homeostasis of the cardiovascular system. It has been established that a dysfunction or damage to the vascular endothelium is the cause of cardiovascular pathologies and complications.

Extracellular nucleotides such as ADP and ATP activate signaling pathways involved in endothelial function (vasomotricity, permeability, cell adhesion, etc.) [1]

In this project, we will study the nucleotide signaling of the vascular endothelium, in particular pathways mediated by High Density Lipoprotein (HDL) and involving cell surface ATP synthase, whose hydrolytic activity generates extracellular ADP which activates P2Y purinergic receptors [2,3]. The translational research part of the project will consist to a preclinical assessment of a novel class of molecules targeting nucleotide signaling pathway to restore endothelial function.

References:

1. Cabou, C.; Martinez, L.O. The Interplay of Endothelial P2Y Receptors in Cardiovascular Health: From Vascular Physiology to Pathology. Int. J. Mol. Sci. 2022, 23, 5883.
2. Cabou, C.; Honorato, P.; Briceño, L.; Ghezali, L.; Duparc, T.; León, M.; Combes, G.; Frayssinhes, L.; Fournel, A.; Abot, A.; et al. Pharmacological inhibition of the F1-ATPase/P2Y1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation. Acta Physiol. 2019, 226, e13268.
3. Martinez, L.O.; Najib, S.; Perret, B.; Cabou, C.; Lichtenstein, L. Ecto-F1-ATPase/P2Y pathways in metabolic and vascular functions of high density lipoproteins. Atherosclerosis 2015, 238, 89–100.

Desired qualification:

• Molecular, biochemical and cellular imaging methods
• Functional in-vitro and in-vivo methods in mouse to assess endothelial functions (e.g. nitric oxide production, endothelial -healing and aortic ring vasorelaxation)
• In-situ hybridation and laser capture microdissection
• Isolation and culture of mouse aortic endothelial cells
• Sc-RNA-seq and scATAC-seq
• Research certificate and accreditation in experimental animal care and use would be a plus
• Knowledge in thromboembolic stroke

Personal qualities:

• High levels of initiative, autonomy and the ability to assume a high level of responsibilit
• Personal suitability, good communication and teamwork skills, inventiveness, and a proactive approach, will be emphasized in the evaluation as well as relevant practical experience. The Postdoctoral Fellow will be expected to contribute to an active research community that promotes the personal and professional growth.
• The position places great demands on the applicant’s capacity for independent goal-oriented work, ability to concentrate and attention to detail.
• In return, Dr Martinez is committed to provide the training and resources needed for the lab members to achieve their goals at any point in their career path in an inclusive and inspirational environment.

Eligibility criteria:

• PhD in biology
• Publication record
• All nationalities

The objectives are:

• To study the phenotpye of endothelial specific transgenic mouse models for P2Y receptors (models already available in the lab.)
• To study, at a pre-clinical stage, the mecanism of action and efficacy of a novel class of molecules targeting nucleotide signaling in endothelial function.