"Intracellular and extracellular inflammatory mediators in carcinogenesis"

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Tel : +33(0)4 92 03 12 23 

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Our research interest

Chronic inflammation can promote tumor development. It is clear that both intracellular and extracellular mediators can enhance chronic inflammation. The main goal of our work is to elucidate which downstream intracellular signalings participate to epithelial cell homeostasis both in inflammatory condition and inflammatory-associated carcinogenesis.

Our projects are based on in vitro, in vivo and human ex vivo models. This allows understanding, manipulating and functional deciphering of selected candidates involved in physiological and pathological inflammation, with the ultimate goal of facilitating the development of new therapeutics.

Research Program

The purinergic P2RX7 receptor is a multimeric protein involved in modulation of various cellular responses (cation exchange,  cell permeability and inflammatory responses) in response to high concentration of extracellular ATP.

We found that P2RX7 receptor deficiency unexpectedly

enhanced tumor formation in a mouse model of

colitis-associated cancer. This result highlights P2RX7

implication in the shaping of the inflammatory

microenvironment and in the control of cell proliferation

and cell death.

We are currently addressing the following questions:


1- How P2RX7 shapes inflammatory microenvironment ? We combine complementary approaches based on bone marrow chimera and conditional tissue specific mouse models to identify the cellular and molecular partners of P2RX7.

2- How P2RX7 mediates anti tumoral effect ? We engineered in vitro cellular models to characterize P2RX7 downstream signaling pathways.

3- Which P2RX7 variants are expressed in human and how these variants mediate human pathologies ? We establish a comprehensive P2RX7 expression map using Sequenom massArray and Tissue Microarrray technologies.

This project is granted by the "Institut National du Cancer" (INCa).

Research Team

DOUGUET Laetitia, Post-Doc

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BENZAKEN Jonathan, M2-Doctor

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JUHEL Thierry, Technician INSERM

Tel : +33(0)4 92 03 12 43, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Former Staff :

Etienne Boulter joined our lab in 2000 and received his PhD in 2004. From 2005 to 2010

he had a post-doctoral position at the University of North Carolina (K. Burridge lab)

and from 2010 to 2013 at the IRCAN (C. Feral lab). Etienne is actually a “chargé de recherche”


Gaelle Cane joined our lab in 2006 and received her PhD in 2009. From 2009 to 2011

she had a research assistant position at Novartis. Then she moved to University of Uppsala.

Dr Abderrahman Chargui, joined our lab in 2010 for a post-doctoral position. Now he has

a permanent position at the University of Tunis.

Sanda Mimouna joined our lab in 2010 and received her PhD in 2013.  After her PhD,

Sanda moved to the Mount Sinai Hospital (S. Dahan lab) for a post-doctoral position.


Hofman P, Cherfils-Vicini J, Bazin M, Ilie M, Juhel T, Hébuterne X, Gilson E, Schmid-Alliana A,

Boyer P, Adriouch S, Vouret-Craviari V.

Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens inflammation

but increases tumor incidence in a mouse model of colitis-associated cancer.

Cancer Res., 2015, 75,:835-45.

Mimouna S, Bazin M, Mograbi B, Darfeuille-Michaud A, Brest P, Hofman P, Vouret-Craviari V.

HIF1A regulates xenophagic degradation of Adherent and Invasive Escherichia coli (AIEC).

Autophagy, 2014, 10:2333-2345.

Belaid A, Cerezo M, Chargui A, Corcelle-Termeau E, Pedeutour F, Giuliano S, Ilie M,

Rubera I, Tauc M, Barale S, Bertolotto C, Brest P, Vouret-Craviari V, Klionsky DJ, Carle GF,

Hofman P, Mograbi B.

Autophagy plays a critical role in the degradation of active RHOA, the control of cell cytokinesis

and genomic stability.

Cancer Res., 2013, Jul 15;73(14):4311-22. 

Chargui A, Cesaro A, Mimouna S, Fareh M, Brest P, Naquet P, Darfeuille-Michaud A, Hébuterne X,

Mograbi B*, Hofman P*, Vouret-Craviari V.

Subvertion of autophagy in adherent invasive E. coli-infected neutrophils induces inflammation

and cell death.

PlosOne, 2012, 7, e51717.

Hofman P, Vouret-Craviari V.

Microbe-induced transcription factors pave the road for inflammation to cancer transition.

Gut Microbes, 2012, 1:3.

Abderrahman C, Mimouna S, Brest P, Hofman P, Vouret-Craviari V.

Epithelial to Mesenchymal Transition in Microbial Pathogenesis, In : Cytokeratins - Tools in

Oncology, Dr. Gerhard Hamilton (Ed.), ISBN: 978-953-51-0047-8, InTech, 2012.

Mimouna S, Gonçalvès D, Barnich N, Darfeuille-Michaud A, Hofman P, Vouret-Craviari V.

Crohn’s disease-associated E. coli promote gastrointestinal inflammatory disorders by

activation of HIF-dependent responses.

Gut Microbes, 2011, 2:6.

Brest P, Lapaquette P, Barbry P, Hebuterne X, Moniers JF, Cesaro A, Vouret-Craviari V, Mograbi B,

Darfeuille-Michaud A, Hofman P.

A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation

of IRGM-dependent xenophagy.

Nature Genetics, 2011, 43:242-245.

Cane G, Ginouvès A, Buscà R, Pouysségur J, Berra E, Hofman P, Vouret-Craviari V.

Afa/Dr Diffusely Adhering E. coli-induced HIF-1a triggers IL 8 and VEGF expression and

promotes EMT-like behaviour.

Cellular Microbiology, 2010, 12:640-653.

Brest P, Corcelle E, Cesaro A, Chargui A, Belaïd A, Klionsky J, Vouret-Craviari V, Hébuterne X,

Hofman P, Mograbi B.

Autophagy and Crohn’s disease: at the crossroad of infection, inflammation, immunity and cancer.

Curr. Mol. Med., 2010, 10:486-502.

Cesaro A, Brest P, Hofman V, Hébuterne X, Wildman S, Ferrua B, Marchetti S, Doglio A,

Vouret-Craviari V, Galland F, Naquet P, Mograbi B, Unwin R, Hofman P.

Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal

epithelial cells in response to neutrophil transepithelial migration.

AJP, 2010, 296:G1332-1343.

Financial Grants

Résultat de recherche d'images pour "logo INCA"