Date de dernière mise à jour : le 6 janvier 2016
Fonction : Doctorante Monitrice - PhD Student
Thèmes de recherche :
My PhD project consists of a study of pro- and antioxidant mechanisms implied in sickle Townes mice through two different approaches.
Sickle cell disease (SCD) is a severe hemoglobinopathy that produces multisystem complications due to the expression of abnormal oxygen-carrying hemoglobin molecule (HbS) leading to rigid sickle-like shaped red blood cells under deoxygenation condition. This disease is characterized by an imbalance between the production of Reactive Oxygen Species (ROS) and antioxidants.
- Pharmacological modulation of oxidative stress
The first part of my work will focus on two oxidative stress actors: the Receptor of Advanced Glycation End-products (RAGE), which are a well-known marker of oxidative stress and Nrf2, a key transcription factor of antioxidant enzymes. To understand their implication in SCD, I will investigate their respective mechanistic pathways through a pharmacological modulation of those two molecules in sickle Townes mice.
- Modulation of oxidative stress through regular physical activity
Acute exercise is usually contra-indicated in SCD patients, as it is likely to generate and amplify the pathophysiology of the disease (tissue hypoxia, increased blood viscosity, inflammation, ROS production, oxidative stress …). However, regular physical activity is a genuine therapeutic approach in numerous pathologies (such as cardiovascular diseases, diabetes, cancers, osteoporosis…) as it increases the recruitment and the formation of capillaries, improves local vasodilation, blunts oxidative stress and inflammatory processes and also activates the Nrf2-antioxidant signaling. Based on that, we hypothesized that moderate exercise training could blunt oxidative stress and thus improve pathophysiology of SCD. So the second part of my PhD’s project is to determine the effect of a 8-week treadmill training on the oxidative stress in Townes sickle mice, in focussing on the Nrf2 pathway.
This work is conducted in collaboration with Solomon Ofori Acquah’s lab at the Vascular Medicine Institute (VMI; http://www.vmi.pitt.edu/labs/oforiacquahlab.html), University of Pittsburgh, Pennsylvania, USA.
Mots clés : Sickle Cell Disease, Physical Activity, Oxidative Stress, Townes mice
2015-3. Martin C, Pialoux V, Faes C, Charrin E, Skinner S, Connes P. Does Physical Activity Increase or Decrease the Risk of Sickle Cell Disease Complications? Br J Sports Med. In Press
2015-2. Faes C, Charrin E, Connes P, Pialoux V, Martin C. Chronic physical activity limits blood rheology alterations in transgenic SAD mice. Am J Hematol. 90 (2): E32-3
2015-1. Charrin E, Aufradet E, Douillard A, Romdhani A, De Souza G, Bessaad A, Faes C, Chirico EN, Pialoux V, Martin C. Oxidative stress is decreased in physically active sickle cell SAD mice. Br J Haematol. 168 (5): 747-56
2014. Aufradet E, Douillard A, Charrin E, Romdhani A, De Souza G, Bessaad A, Faes C, Bourgeaux V, Chirico EN, Canet-Soulas E, Pialoux V, Martin C. Physical activity limits pulmonary endothelial activation in sickle cell SAD mice. Blood. 123 (17): 2745-7
2014. Charrin E, Romdhani A, Aufradet E, Pialoux V, Martin C. Effects of physical activity on oxidative stress and vascular adhesion modulators after a hypoxia/reoxygenation stress in sickle SAD mice. 9th European Congress on sickle cell disease. Strasbourg, 6-8 Mars 2014
2015. Charrin E, Martin C, Dube J, Connes Philippe, Pialoux V, Ofori-Acquah S. Moderate exercise training attenuates inflammation in transgenic sickle cell mice. 57th American Society of Hematology Annual Meeting. Orlando, FL, USA, 5-8 Décembre 2015
2015. Charrin E, Ofori-Acquah S, Faes C, Connes P, Pialoux V et Martin C. Effets anti-inflammatoires d’un entrainement à intensité modérée chez des souris drépanocytaires Townes. 20ème Journée de l’EDISS. Lyon. 18 Octobre 2015.
2015. Charrin E, Ofori-Acquah S, Faes C, Connes P, Pialoux V et Martin C. Effets anti-inflammatoires d’un entrainement à intensité modérée chez des souris drépanocytaires Townes. Congrès du Club du Globule Rouge et du Fer. Arcachon. 24-25 Septembre 2015.