Leader
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Paradis Valérie
- 01 40 87 54 63
- valerie.paradis@bjn.aphp.fr
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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 : 16 December 2022 More
Autors : Klaus Seedorf Csaba Weber Cedric Vinson Sylvie Berger Laurent-Michel Vuillard Arpad Kiss Stephanie Creusot Olivier Broux Anne Geant Catherine Ilic Karine Lemaitre Johann Richard Hammoutene Adel Julien Mahieux Virginie Martigny Didier Durand Fabien Melchiore Miklos Nyerges Paradis Valérie Nicolas Provost Valérie Duvivier Philippe Delerive
Publication date : 01 September 2022 More
Autors : De Mestier Louis Nicolle Rémy Poté Nicolas Rebours Vinciane Cauchy François Olivia Hentic Frédérique Maire Ronot Maxime Lebtahi Rachida Sauvanet Alain Paradis Valérie Ruszniewski Philippe Couvelard Anne Cros Jérome
Publication date : 25 July 2022 More
Autors : Romain Donne Maëva Saroul-Ainama Pierre Cordier Hammoutene Adel Christelle Kabore Mira Stadler Ivan Nemazanyy Isabelle Galy-Fauroux Mounia Herrag Tobias Riedl Marie Chansel-Da Cruz Stefano Caruso Stéphanie Bonnafous Rupert Öllinger Roland Rad Kristian Unger Albert Tran Jean-Pierre Couty Philippe Gual Paradis Valérie Séverine Celton-Morizur Mathias Heikenwalder Patrick Revy Chantal Desdouets
Publication date : 31 March 2022 More
Autors : Valérie Duvivier Stéphanie Creusot Olivier Broux Aurélie Helbert Ludovic Lesage Kevin Moreau Nicolas Lesueur Lindsay Gerard Karine Lemaitre Nicolas Provost Edwige-Ludiwyne Hubert Tania Baltauss Brzustowski Angélique Nathalie De Preville Julia Geronimi Lucie Adoux Franck Letourneur Hammoutene Adel Valla Dominique Paradis Valérie Philippe Delerive
Publication date : 11 February 2022 More
Autors : Patricia Sansilvestri Morel Valerie Duvivier Florence Bertin Nicolas Provost Hammoutene Adel Edwige-Ludiwyne Hubert Arantxa Gonzalez Isabelle Tupinon-Mathieu Paradis Valérie Philippe Delerive
Publication date : 01 February 2022 More
Autors : Beaufrère Aurélie Stefano Caruso Julien Calderaro Poté Nicolas Jean-Charles Bijot Gabielle Couchy Cauchy François Vilgrain Valérie Jessica Zucman-Rossi Paradis Valérie
Publication date : 28 November 2021 More
Autors : Couvineau Alain Voisin Thierry Nicole Pascal Gratio Valérie Anne Blais
Publication date : 01 July 2021 More
Autors : Ahmed Montasser Beaufrère Aurélie Cauchy François Mohamed Bouattour Soubrane Olivier ALBUQUERQUE Miguel Paradis Valérie
Publication date : 29 June 2021 More
Autors : Sophie Chopinet Cauchy François Christian Hobeika Beaufrère Aurélie Poté Nicolas Farges Olivier Dokmak Safi Mohamed Bouattour Ronot Maxime Vilgrain Valérie Paradis Valérie Soubrane Olivier
Publication date : 11 March 2021 More
Autors : Raffenne Jérome Fernando A Martin Rémy Nicolle Marina Konta Yuna Blum Jérôme Torrisani Francesco Puleo Jean Baptiste Bachet Magali Svrcek Armel Bardier-Dupas Jean Francois Emile Peter Demetter Miroslav Radman Jean Luc Van Laethem Hammel Pascal Rebours Vinciane Paradis Valérie Couvelard Anne Cros Jérome
Publication date : 28 August 2020 More
Autors : Guedj Nathalie Lorraine Blaise Cauchy François ALBUQUERQUE Miguel Soubrane Olivier Paradis Valérie
Publication date : 24 August 2020 More
Autors : Elia Gigante Paradis Valérie Ronot Maxime Cauchy François Soubrane Olivier Nathalie Ganne-Carrié Jean-Charles Nault
Publication date : 01 March 2020 More
Autors : Hammoutene Adel Biquard Louise Juliette Lasselin Marouane Kheloufi Tanguy Marion Anne-Clémence Vion Jules Mérian Nathalie Colnot Xavier Loyer Alain Tedgui Patrice Codogno Lotersztajn Sophie Paradis Valérie Chantal M Boulanger Rautou Pierre-Emmanuel
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 : 01 May 2019 More
Autors : Cindy Neuzillet Annemilaï Tijeras-Raballand Chanthirika Ragulan Cros Jérome Yatish Patil Matthieu Martinet Mert Erkan Jörg Kleeff Jeremy Wilson Minoti Apte Marie Tosolini Abigail S Wilson Francesca R Delvecchio Corinne Bousquet Paradis Valérie Hammel Pascal Anguraj Sadanandam Hemant M Kocher
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 : 21 January 2019 More
Autors : Nicolle Rémy Raffenne Jérome Paradis Valérie Couvelard Anne Aurelien de Reynies Yuna Blum Cros Jérome
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 : 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 : 01 April 2018 More
Autors : Poté Nicolas Cauchy François ALBUQUERQUE Miguel Cros Jérome Soubrane Olivier Bedossa Pierre Paradis Valérie