Our team investigates the signaling pathways that are activated by environmental pollutants and, in particular, dioxins, pesticides, alcohol and their mixtures. Our main focus is a transcription factor, the Aryl hydrocarbon Receptor (or AhR), which is activated following its binding to these xenobiotics. This protein triggers the transcription of xenobiotic metabolizing enzymes, which allow the detoxification of the ligands and their elimination from the body. Our work has shown, however, that the AhR regulates many other functions:
1) We have demonstrated, using tumor cell lines, that TCDD (the most well-studied dioxin) stimulates an epithelial-mesenchymal transition which could contribute to pathological processes such as a) tumor metastasis (clinical investigations are underway); b) chronic liver diseases including steatosis and fibrosis (studied with murine models).
2) The mixture TCDD and a-endosulfan alters the expression of enzymes which are involved in the metabolism primarily of carbohydrates, lipids and alcohol. The change in the expression of these enzymes results in a metabolic disruption (ex: Warburg effect) which could be responsible for the previously cited pathological proceesses. At present, we are investigating the effects of such mixtures of pollutants using both proteomic and metabolomic technologies (HEALS European project).
3) Adipose tissue stores and releases hydrophobic pollutants and a significant part of our work is dedicated to the study of the effects of xenobiotics on adipose tissue metabolism.
4) We discovered and continue to investigate the visio-motor abnormalities in AhR knockout mice which are present in the absence of pollutants. These abnormities suggest that the AhR protein plays a role in ocular stability.
5) Diverse functional effects may arise from a structural flexibility in the AhR which permits its binding to diverse ligands. We collaborate with the group of Dr. Pierre Nioche (Crystallography group at the University Paris Descartes) to elucidate the mechanisms by which ligand induced structural alterations in the AhR lead to these diverse functional effects.
- Novel roles for AhR and ARNT in the regulation of alcohol dehydrogenases in human hepatic cells.
Attignon EA, Leblanc AF, Le-Grand B, Duval C, Aggerbeck M, Rouach H, Blanc EB : Arch Toxicol, 2016
- Regulation of Aquaporin 3 expression by the AhR pathway is critical to cell migration.
Linh-Chi B, Céline T, Stephane P, Aline C, Robert B, Xavier C : Toxicol Sci, 2015
- Associations of plasma concentrations of dichlorodiphenyldichloroethylene and polychlorinated biphenyls with prostate cancer: a case-control study in Guadeloupe (French West Indies).
Emeville E, Giusti A, Coumoul X, Thomé JP, Blanchet P, Multigner L : Environ Health Perspect, 2014
- Activation of the aryl hydrocarbon receptor by carcinogenic aromatic amines and modulatory effects of their N-acetylated metabolites.
Juricek L, Bui LC, Busi F, Pierre S, Guyot E, Lamouri A, Dupret JM, Barouki R, Coumoul X, Rodrigues-Lima F : Arch Toxicol, 2014
- Aryl hydrocarbon receptor-dependent induction of liver fibrosis by dioxin.
Pierre S, Chevallier A, Teixeira-Clerc F, Ambolet-Camoit A, Bui LC, Bats AS, Fournet JC, Fernandez-Salguero P, Aggerbeck M, Lotersztajn S, Barouki R, Coumoul X : Toxicol Sci, 2013
- Oculomotor deficits in aryl hydrocarbon receptor null mouse.
Chevallier A, Mialot A, Petit JM, Fernandez-Salguero P, Barouki R, Coumoul X, Beraneck M : PLoS One, 201
- Early-life prevention of non-communicable diseases
Balbus JM, Barouki R, Birnbaum LS, Etzel RA, Gluckman PD, Grandjean P, Hancock C, Hanson MA, Heindel JJ, Hoffman K, Jensen G, Keeling A, Neira M, Rabadan-Diehl C, Ralston J, Tang KC : Lancet, 2013
- The aryl hydrocarbon receptor regulates focal adhesion sites through a non-genomic FAK/Src pathway.
Tomkiewicz C, Herry L, Bui LC, Métayer C, Bourdeloux M, Barouki R, Coumoul X : Oncogene, 2012
- Inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells.
Kim MJ, Pelloux V, Guyot E, Tordjman J, Bui LC, Chevallier A, Forest C, Benelli C, Clément K, Barouki R : Environ Health Perspect, 2012
- Identification of a new stilbene-derived inducer of paraoxonase 1 and ligand of the Aryl hydrocarbon Receptor.
- Guyot E, Coumoul X, Chassé JF, Khallouki F, Savouret JF, Poirot M, Barouki R : Biochem Pharmacol, 2012
- Fate and complex pathogenic effects of dioxins and polychlorinated biphenyls in obese subjects before and after drastic weight loss.
Kim MJ, Marchand P, Henegar C, Antignac JP, Alili R, Poitou C, Bouillot JL, Basdevant A, Le Bizec B, Barouki R, Clément K : Environ Health Perspect, 2011
- Induction of the Ras activator Son of Sevenless 1 by environmental pollutants mediates their effects on cellular proliferation.
Pierre S, Bats AS, Chevallier A, Bui LC, Ambolet-Camoit A, Garlatti M, Aggerbeck M, Barouki R, Coumoul X : Biochem Pharmacol, 2010
Barouki R, Melén E, Herceg Z, Beckers J, Chen J, Karagas M, Puga A, Xia Y, Chadwick L, Yan W, Audouze K, Slama R, Heindel J, Grandjean P, Kawamoto T, Nohara K : Environ Int, 2018
Audouze K, Taboureau O, Grandjean P : Toxicol Appl Pharmacol, 2018
Shackleford G, Sampathkumar NK, Hichor M, Weill L, Meffre D, Juricek L, Laurendeau I, Chevallier A, Ortonne N, Larousserie F, Herbin M, Bièche I, Coumoul X, Beraneck M, Baulieu EE, Charbonnier F, Pasmant E, Massaad C : Proc Natl Acad Sci U S A, 2018
Taboureau O, Audouze K : ALTEX, 2017
Boezio B, Audouze K, Ducrot P, Taboureau O : Mol Inform, 2017
Attignon EA, Distel E, Le-Grand B, Leblanc AF, Barouki R, de Oliveira E, Aggerbeck M, Blanc EB : Toxicol In Vitro, 2017
Juricek L, Carcaud J, Pelhaitre A, Riday TT, Chevallier A, Lanzini J, Auzeil N, Laprévote O, Dumont F, Jacques S, Letourneur F, Massaad C, Agulhon C, Barouki R, Beraneck M, Coumoul X : Sci Rep, 2017