From H2O2 generator DUOX to oxidative stress and cancer development


Abstract : Hydrogen peroxide (H2O2) is a highly reactive chemical molecule originally considered as an antibacterial agent. In excess, H2O2 induces an oxidative stress responsible for different pathologies like cardiovascular disease, tumorigenesis or ageing. It is now widely accepted that many cell types other than the phagocytes produce reactive oxygen species (ROS). The thyroid tissue generates massive amounts of H2O2 that are required for the biosynthesis of thyroid hormones T3/T4. In 2000, we discovered and characterized the molecular nature of the molecules responsible for this H2O2 generating system: the DUOX1 and DUOX2 enzymes. These proteins belong to a new family of proteins, the NADPH-oxidases, presenting a catalytic domain involved in ROS generation. The DUOX are also present at the mucosal surface of the digestive and respiratory epithelia. Our multidisciplinary projects aim to better characterize the function of these new oxidases and to study their physiological roles in humans using DUOX knock-out mouse models as well as novel transgenic mouse models overexpressing these oxidases. By molecular and biochemical approaches, we also explore the mechanisms involved in their maturation and function. A better understanding of the biochemistry of these new H2O2 generators would have a major impact in the comprehension of the pathophysiology of ROS-mediated diseases.
Promoteur/Supervisor : Prof. DE DEKEN Xavier
Email : xdedeken@ulb.ac.be
Site Web/Web site : http://duoxlab.iribhm.org/
Centre de recherche/Research center : IRIBHM - DUOX Lab
Faculté/Faculty : Faculty of Medicine/Faculté de Médecine
Ecole doctorale/Graduate Colleges : Biomedical and Pharmaceutical Science/Sciences biomédicales et pharmaceutiques
Ecole doctorale thématique/Graduate School (French Only): Biologie Cellulaire et Moléculaire, Biochimie (BCMB)



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