Mini CV2001-2004: PhD Biology and Health, Bordeaux University, France
2005-2006: Posdoctoral fellow, French Atomic Energy Commission (CEA), Fontenay aux Roses, France 2006-2009: Posdoctoral fellow, INSERM, Toulouse, France 2010-2012: Posdoctoral fellow, Harvard Medical School MGH, Boston MA, USA 2012-2013: Instructor, Harvard Medical School MGH, Boston MA, USA 2013-present: Permanent researcher (CR1), INSERM, Toulouse, France |
expertiseExpertise in molecular biology
Use of multiple murine models |
RECHERCHE/PROJET RESEARCH/PROJECT
Caractérisation de la Matriptase-2, une protéase essentielle au métabolime du fer
La matriptase-2 est une protéase essentielle pour le maintien de l’homéostasie du fer. Une mutation dans le gène codant pour la matriptase-2 conduit à une maladie génétique humaine IRIDA caractérisée par une anémie et une déficience en fer sévères.
Le projet de recherche que nous développons vise d’une part à caractériser le rôle exact et le mécanisme d’action de cette protéase en identifiant ses cibles et ses inhibiteurs endogènes et d’autre part à identifier des petites molécules inhibitrices de son activité dans le but de corriger la surcharge en fer associée à deux maladies génétiques : l’hémochromatose et la thalassémie.
En parallèle, un projet de recherche focalisé sur la stéatose-hépatique-non-alcoolique est développé afin d’évaluer le rôle du fer dans la sévérité de cette maladie.
Characterization of Matriptase-2, an essential protease for iron homeostasis
Matriptase-2 is an essential protease for the regulation of iron homeostasis. In humans, mutations in the gene encoding for matriptase-2 lead to a genetic disorder (IRIDA) characterized by a severe anemia and an iron deficiency.
The research project that we are currently developing aims on the one hand to characterize the exact role and the mechanism of action of this protease by identifying its targets and endogenous inhibitors and on the other hand to identify small molecules inhibitor of its activity to correct the iron overload associated with two genetic diseases: hemochromatosis and thalassemia.
In parallel, a research project focused on nonalcoholic fatty liver disease is developed to assess the role of iron in the severity of this disease.
La matriptase-2 est une protéase essentielle pour le maintien de l’homéostasie du fer. Une mutation dans le gène codant pour la matriptase-2 conduit à une maladie génétique humaine IRIDA caractérisée par une anémie et une déficience en fer sévères.
Le projet de recherche que nous développons vise d’une part à caractériser le rôle exact et le mécanisme d’action de cette protéase en identifiant ses cibles et ses inhibiteurs endogènes et d’autre part à identifier des petites molécules inhibitrices de son activité dans le but de corriger la surcharge en fer associée à deux maladies génétiques : l’hémochromatose et la thalassémie.
En parallèle, un projet de recherche focalisé sur la stéatose-hépatique-non-alcoolique est développé afin d’évaluer le rôle du fer dans la sévérité de cette maladie.
Characterization of Matriptase-2, an essential protease for iron homeostasis
Matriptase-2 is an essential protease for the regulation of iron homeostasis. In humans, mutations in the gene encoding for matriptase-2 lead to a genetic disorder (IRIDA) characterized by a severe anemia and an iron deficiency.
The research project that we are currently developing aims on the one hand to characterize the exact role and the mechanism of action of this protease by identifying its targets and endogenous inhibitors and on the other hand to identify small molecules inhibitor of its activity to correct the iron overload associated with two genetic diseases: hemochromatosis and thalassemia.
In parallel, a research project focused on nonalcoholic fatty liver disease is developed to assess the role of iron in the severity of this disease.
PRODUCTION SCIENTIFIQUE SCIENTIFIC PRODUCTION
1. Nai A, Rubio A, Campanella A, Gourbeyre O, Artuso I, Bordini J, Gineste A, Latour C, Besson-Fournier C, Lin HY, Coppin H, Roth MP, Camaschella C, Silvestri L and Meynard D. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.(2016). Blood. 127(19):2327-36
2. Latour C, Besson-Fournier C, Meynard D, Silvestri L, Gourbeyre O, Aguilar-Martinez P, Schmidt PJ, Fleming MD, Roth MP, Coppin H. Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin. (2016) Hepatology;63(1):126-137.
3. Zumbrennen-Bullough KB,…, Meynard D, et al. MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. (2014) J Biol Chem. Aug 22;289(34):23796-23808.
4. Wang CY, Meynard D, Lin HY. The role of TMPRSS6/matriptase-2 in iron regulation and anemia. (2014), Frontiers in pharmacology;5:114.
5. Meynard D, Babitt JL, Lin HY. The liver: conductor of systemic iron balance. (2014) Blood;123(2):168-176
6. Meynard D, Sun CC, Wu Q, Chen W, Chen S, Nelson CN, Waters MJ, Babitt JL, Lin HY(2013) Inflammation Regulates TMPRSS6 Expression via STAT5. PLoS One 8(12):e82127.
7. Chen W, Sun CC, Chen S, Meynard D, Babitt JL, Lin HY.(2013) A novel validated enzyme-linked immunosorbent assay to quantify soluble hemojuvelin in mouse serum. Haematologica. 98(2):296-304
8. Corradini E, Rozier M, Meynard D, Odhiambo A, Lin HY, Feng Q, Migas MC, Britton RS, Babitt JL, Fleming RE. (2011). Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe. Gastroenterology. 141(5):1907-1914
9. Meynard D, Vaja V, Sun CC, Corradini E, Chen S, López-Otín C, Grgurevic L, Hong CC, Stirnberg M, Gütschow M, Vukicevic S, Babitt JL, Lin HY. (2011). Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood. 118(3):747-56
10. Corradini E, Meynard D, Wu Q, Chen S, Ventura P, Pietrangelo A, Babitt JL. (2011). Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology. 54(1):273-84
11. Kautz L, Besson-Fournier C, Meynard D, Latour C, Roth MP, Coppin H. (2011). Iron overload induces BMP6 expression in the liver but not in the duodenum. Haematologica. 96(2):199-203
12. Corradini E, Schmidt PJ, Meynard D, Garuti C, Montosi G, Chen S, Vukicevic S, Pietrangelo A, Lin HY, Babitt JL. (2010). BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice. Gastroenterology. 139(5):1721-9
13. Kautz L, Meynard D, Besson-Fournier C, Darnaud V, Al Saati T, Coppin H, Roth MP. (2009). BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood. 17;114(12):2515-20
14. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. (2009). Lack of Bone Morphogenetic Protein BMP6 induces massive iron overload. Nat Genet. 41(4):478-81
15. Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R, Wang RH, Deng C, Vaulont S, Mosser J, Coppin H, Roth MP. (2008). Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood, 112 : 1503-9.
16. Coppin H, Darnaud V, Kautz L, Meynard D, Aubry M, Mosser J, Martinez M, Roth MP. (2007). Gene expression profiling of Hfe-/- liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers. Genome Biol, 8 : R221.
17. Saintigny Y, Roche S, Meynard D, Lopez BS. (2008). Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium. Radiat Res, 170 : 172-83
18. Meynard D, Le Morvan V, Bonnet J, Robert J. (2007). Functional analysis of the gene expression profiles of colorectal cancer cell lines in relation to oxaliplatin and cisplatin cytotoxicity. Oncol Rep, 17 : 1213-21.
19. Charasson V, Bellott R, Meynard D, Longy M, Gorry P, Robert J. (2004). Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38. Clin Pharmacol Ther, 76 : 528-35.
20. Vekris A, Meynard D, Haaz MC, Bayssas M, Bonnet J, Robert J. (2004). Molecular determinants of the cytotoxicity of platinum compounds: the contribution of in silico research. Cancer Res, 64 : 356-62
2. Latour C, Besson-Fournier C, Meynard D, Silvestri L, Gourbeyre O, Aguilar-Martinez P, Schmidt PJ, Fleming MD, Roth MP, Coppin H. Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin. (2016) Hepatology;63(1):126-137.
3. Zumbrennen-Bullough KB,…, Meynard D, et al. MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. (2014) J Biol Chem. Aug 22;289(34):23796-23808.
4. Wang CY, Meynard D, Lin HY. The role of TMPRSS6/matriptase-2 in iron regulation and anemia. (2014), Frontiers in pharmacology;5:114.
5. Meynard D, Babitt JL, Lin HY. The liver: conductor of systemic iron balance. (2014) Blood;123(2):168-176
6. Meynard D, Sun CC, Wu Q, Chen W, Chen S, Nelson CN, Waters MJ, Babitt JL, Lin HY(2013) Inflammation Regulates TMPRSS6 Expression via STAT5. PLoS One 8(12):e82127.
7. Chen W, Sun CC, Chen S, Meynard D, Babitt JL, Lin HY.(2013) A novel validated enzyme-linked immunosorbent assay to quantify soluble hemojuvelin in mouse serum. Haematologica. 98(2):296-304
8. Corradini E, Rozier M, Meynard D, Odhiambo A, Lin HY, Feng Q, Migas MC, Britton RS, Babitt JL, Fleming RE. (2011). Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe. Gastroenterology. 141(5):1907-1914
9. Meynard D, Vaja V, Sun CC, Corradini E, Chen S, López-Otín C, Grgurevic L, Hong CC, Stirnberg M, Gütschow M, Vukicevic S, Babitt JL, Lin HY. (2011). Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood. 118(3):747-56
10. Corradini E, Meynard D, Wu Q, Chen S, Ventura P, Pietrangelo A, Babitt JL. (2011). Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology. 54(1):273-84
11. Kautz L, Besson-Fournier C, Meynard D, Latour C, Roth MP, Coppin H. (2011). Iron overload induces BMP6 expression in the liver but not in the duodenum. Haematologica. 96(2):199-203
12. Corradini E, Schmidt PJ, Meynard D, Garuti C, Montosi G, Chen S, Vukicevic S, Pietrangelo A, Lin HY, Babitt JL. (2010). BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice. Gastroenterology. 139(5):1721-9
13. Kautz L, Meynard D, Besson-Fournier C, Darnaud V, Al Saati T, Coppin H, Roth MP. (2009). BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood. 17;114(12):2515-20
14. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. (2009). Lack of Bone Morphogenetic Protein BMP6 induces massive iron overload. Nat Genet. 41(4):478-81
15. Kautz L, Meynard D, Monnier A, Darnaud V, Bouvet R, Wang RH, Deng C, Vaulont S, Mosser J, Coppin H, Roth MP. (2008). Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood, 112 : 1503-9.
16. Coppin H, Darnaud V, Kautz L, Meynard D, Aubry M, Mosser J, Martinez M, Roth MP. (2007). Gene expression profiling of Hfe-/- liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers. Genome Biol, 8 : R221.
17. Saintigny Y, Roche S, Meynard D, Lopez BS. (2008). Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium. Radiat Res, 170 : 172-83
18. Meynard D, Le Morvan V, Bonnet J, Robert J. (2007). Functional analysis of the gene expression profiles of colorectal cancer cell lines in relation to oxaliplatin and cisplatin cytotoxicity. Oncol Rep, 17 : 1213-21.
19. Charasson V, Bellott R, Meynard D, Longy M, Gorry P, Robert J. (2004). Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38. Clin Pharmacol Ther, 76 : 528-35.
20. Vekris A, Meynard D, Haaz MC, Bayssas M, Bonnet J, Robert J. (2004). Molecular determinants of the cytotoxicity of platinum compounds: the contribution of in silico research. Cancer Res, 64 : 356-62