CV Science

Alain COUVINEAU PhD Biochemistry, Reasearch director INSERM

Course and current status

Name :    COUVINEAU

Surname : Alain

Lab adress :   Centre de Recherche sur l'Inflammation (CRI)

INSERM 1149

Faculté de Médecine Xavier Bichat

16, Rue H. Huchard

75018 Paris

Diploma :

 1981 Bachelor’s degree of Paris 6 University

 1982 Bachelor’s degree (Biochemistry) of Paris 6 University

 1983 Master‘s degree (Biochemistry) of Paris 6 University

 1984 Master thesis (Pharmacology) of Paris 6 University

1986 PhD of molecular pharmacology of Paris 6 University

Position : 

 1996-  Research Director

 1991-1996   Research Assistant (1^st class)

 1987-1991   Research Assistant (2^nd class)

Assigments:                 

 2010-             INSERM U1149/CRI (R. Monteiro)

 2007- 2009     INSERM U773/CRB3 (M. Laburthe)

 2005-2006      INSERM U683 (M. Laburthe)

 1994-2004      INSERM U410 (M. Laburthe)

 1991-1993      INSERM U239 (F. Potet)

 1984-1990      INSERM U178 (A. Zweibaum)

 1983-1984      INSERM U55 (G. Rosselin)

Research activity:

 2019-         Team leader of “From inflammation to cancer in digestive diseases” INSERM   U1149/CRI.                  

2014-2018   Team leader of “From inflammation to cancer in digestive diseases” INSERM U1149/CRI.

 2009-2013  Team leader of “Membrane receptors :structure, function and physiopathology” INSERM U773/CRB3.

Scientific award:  Jacqueline Besson Award, 1992.

Scientific expert:  

For several international reviews (Peptides, Reg. Peptides, Biochemica. Biophysica. Acta. Am. J. Physiol., Cell Calcium., Oncotarget, Frontier in endocrinology, Breakout Labs, IJMS, Cells (USA)…

Review editor in Frontier in endocrinology section: Molecular and Structural Endocrinology

Editor in IJMS journal (MDPI).

Review Editor in Cells journal (MDPI).

Scientific production:

Co-inventor in 13 patents.

ORCID ID: 0000-0003-2912-5168

Scorpus ID: 7004155396

Researcher ID: G-3641-2013

Loop ID: 66160

Scientific summary

The G protein-coupled receptors (GPCR) constitute the largest family of membrane receptors with more than 800 sequences encoded by about 4% of the human genome. GPCRs, which act as molecule sensors on the cell surface, lead to signal transduction by activation and/or inhibition of various intracellular signaling pathways leading to final cellular responses. The nature of ligands interacting with GPCRs is characterized by a great diversity, including light, ions, amines, lipids, peptides, proteases, small and large proteins having multiple properties as neurotransmitters, hormones, pheromones and odors among others. In that respect, the crosstalk between GPCRs and the actors of inflammation and/or cancer has led to consider these receptors as very promising targets with potential therapeutic applications in inflammatory and cancer pathologies. Among the 800 members of the GPCR family, orexin receptors represent an archetype of a putative target for the treatment of cancers and chronic inflammatory diseases.

Orexins, also known as hypocretins, comprise two neuropeptides isoforms of 33 and 28 aminoacids, orexin A (OXA/hypocretin-1) and orexin B (OXB/hypocretin-2), respectively. They were initially identified by reverse pharmacology as the endogenous ligands for two orphan GPCR subtypes belonging to the class A family, orexin receptor 1 and 2 (OX1R (Hcrt-1) and OX2R (Hcrt-2), respectively). The main signaling pathways that have been associated to orexin receptors is phospholipase/Ca²⁺ pathway. The major biological action of orexins is the regulation of sleep/wakefulness state. Related to this action, one major pathology associated to a deficit of orexin production is narcolepsy. In addition to their ability to modulate sleep and arousal states, these neuropeptides regulate appetite and feeding, gastrointestinal mobility, energy balance and metabolism, but also play a role in cognitive processes.

In 2011, our group had demonstrated that OX1R but not OX2R was highly expressed in colon cancer cell lines and colorectal tumors from patients. Orexins treatment of digestive cancer cell lines derived from colon, pancreas and liver cancers induced a strong cell death by apoptosis. The orexin-induced apoptosis was mediated by the phosphorylation of two tyrosine-based motifs (ITIM) present in the receptor sequence. This triggered successive signaling events   such as: the recruitment of the phosphotyrosine phosphatase SHP2, the phosphorylation of the p38 mitogen/stress-activated protein kinase and the translocation of the proapoptotic protein Bax in the mitochondria, leading to apoptosome formation and caspase (3 and 7) activation. In a preclinical model, where cancer cells lines derived from colon, pancreas, liver and prostate cancers were sub-cutaneously xenografted, OXA treatment induced a strong reduction of tumor volume. This anti-tumoral effect of OXA was also observed in the patient-derived xenograft model. More recently, our group has demonstrated that OX1R is highly expressed in inflamed tissues from human IBD. Orexin via OX1R induced a strong anti-inflammatory response by the secretion inhibition of major cytokines involved in inflammatory process (TNF, IL-6…) of IBD, multiple sclerosis and obesity. Our project is to identify the mechanism of action of the orexin/OX1R system in digestive diseases (cancer and inflammation) and develop a new innovative molecules having a therapeutical interest.