Leader
-
Paradis Valérie
- 01 40 87 54 63
- valerie.paradis@bjn.aphp.fr
-
Couvineau Alain
- 01 57 27 74 88
- alain.Couvineau@inserm.fr
This project results of the merging of 3 research teams from the past 5-years contract and aims to investigate specific aspects of the physiopathology of the sequence inflammation-cancer in digestive tract, identify new diagnostic markers and develop innovative therapeutic targets. First axis, focusing on liver carcinogenesis related to metabolic syndrome, will identify the specific mechanisms involved in inflammatory liver damages by favoring original in situ molecular approaches such as mass spectrometry imaging (MSI). The contribution of lipid environment (liver or visceral adipose tissue) in the progression to hepatocellular carcinoma (HCC) will also be investigated. Second axis will provide new insights in the role of GPCR in the progression of digestive cancers, which will allow the development of new therapeutic strategies. We will focus on (1) orexins and their receptors (OXR) which induce a robust apoptosis in digestive cancers, and (2) CXCR4 which confers survival, invasion potential to cancer cells. We will be especially interested to evaluate potential effects of these targets in preclinical models of digestive cancers that have developed resistance to conventional cytotoxic or targeted therapies.
Research projects:
Work package: Inflammation, fibrosis and cancer in the liver
Metabolic syndrome (MS) is becoming the leading cause of chronic liver diseases worldwide and may result in the development of chronic liver diseases and hepatocellular carcinoma (HCC). Progression of liver carcinogenicity in MS is complex, involving the development of tissue damages (steatosis and fibrosis) and also an inflammatory systemic background through adipokines production from visceral adipose tissue
Our project aims:
This project will be based on the development of innovative technologies including mass spectrometry imaging (MALDI imaging), tissue culture models (ex vivo models) and animal models which reproduced liver damages related to MS (High fat diet, fructose diet …). The determination of molecular species identified by MALDI was carried out in collaboration with JM Camadro’s group (Institut J. Monod, Paris).
Work package: GPCRs and digestive cancers (Couvineau Alain’s group)
Since few years ago, drugs targeting G protein-coupled receptors GPCRs are shown to have excellent therapeutic benefits. In this context, our project is to study the role and clinical interest of GPCRs in particular orexin receptors (OXR), in digestive cancer development. Orexins, hypothalamic peptides, interacted with two GPCR (OX1R and OX2R). They regulate sleep, wakefulness, feeding, breathing, reward system, or drug addiction. We have shown that orexins induced a robust apoptosis in colon cancer cell lines which expressed OX1R. This cell death was mediated through ITIM sequence resulting in the recruitment and theactivation of the SHP-2, leading to a mitochondrial apoptosis. Furthermore, we have demonstrated that OX1R is aberrantly expressed in digestive cancers including colon cancers, pancreas cancers and liver cancers but inversely is not present in normal tissue. Moreover we have demonstrated that orexins have strong anti-tumoral effects in pre-clinical models of digestive cancers.
Our project aims:
This project could lead :
3D model of OX1R
Publication date : 13 January 2020 More
Autors : Poté Nicolas Cros Jérome Laouirem Samira Raffenne Jérome Negrão M ALBUQUERQUE Miguel Bedossa Pierre Godinho Ferreira M Ait Si Ali S Fior R Paradis Valérie
Publication date : 31 December 2019 More
Autors : Gigante E Ronot Maxime Bertin C Ciolina M Bouattour M Dondero F Cauchy F Soubrane Olivier Paradis Valérie
Publication date : 19 December 2019 More
Autors : Hobeika C Ronot Maxime Beaufrere A Paradis Valérie Soubrane Olivier Cauchy F
Publication date : 18 November 2019 More
Autors : Raffenne Jérome Nicolle R Puleo F Le Corre D Boyez C Marechal R Emile JF Demetter P Bardier A Laurent-Puig P De Mestier Louis Paradis Valérie Couvelard Anne VanLathem JL MacKey JR Bachet JB Svrcek M Cros Jérome
Publication date : 01 April 2019 More
Autors : Laouirem Samira Sannier A Norkowski E Cauchy F Doblas Sabrina Rautou Pierre-Emmanuel ALBUQUERQUE Miguel Garteiser Philippe Sognigbé L Raffenne Jérome Van Beers Bernard Soubrane Olivier Bedossa Pierre Cros Jérome Paradis Valérie
Publication date : 01 January 2019 More
Autors : Le Faouder Julie Gigante E Léger T ALBUQUERQUE Miguel Beaufrère A Soubrane Olivier Dokmak S Camadro JM Cros Jérome Paradis Valérie
Publication date : 02 November 2018 More
Autors : Rebours Vinciane Garteiser Philippe Ribeiro-Parenti Lara Cavin JB Doblas Sabrina Page Gwenael Bado André Couvineau Alain Ruszniewski Philippe Paradis Valérie Le Gall Maude Van Beers Bernard Couvelard Anne
Publication date : 18 August 2018 More
Autors : Messal N Fernandez N Dayot Stephanie Gratio Valérie Nicole Pascal Prochasson C Chantret Isabelle LeGuilloux G Jarry A Couvelard Anne Treton Xavier Voisin Thierry Ogier-Denis Eric Couvineau Alain
Publication date : 09 January 2018 More
Autors : Dayot Stephanie Speisky D Couvelard Anne Bourgoin P Gratio Valérie Cros Jérome Rebours Vinciane Sauvanet Alain Bedossa Pierre Paradis Valérie Ruszniewski Philippe Couvineau Alain Voisin Thierry