Group leader, Research Director in Inserm
Laboratory: TRADGENE EA4554
« Translational control and gene therapy of vascular diseases »,
Institut des Maladies Métaboliques et Cardiovasculaires,
Université Paul Sabatier, Toulouse
2007-2010 : Inserm U858, Institut de Médecine Moléculaire de Rangueil I2MR (director A. Parini, Dep Dir AC Prats), IFR150, Toulouse
2003-2006 : Inserm U589 (Dir AC Prats), IFR31, CHU Rangueil, Toulouse
1994-2002 : Inserm U397 (Dir F Bayard), IFR31, CHU Rangueil, Toulouse
1990-1994: Laboratoire de Biologie Moléculaire des Eucaryotes (Dir F Amalric), Toulouse
1985-1990 : Laboretro (Dir JL Darlix), CRBGC du CNRS, 118, route de Narbonne, Toulouse
1994 : HDR (Enabling to Direct Research). Paul Sabatier University, Toulouse III.
1988 : Doctorate thesis in Molecular Virology (PhD), Paul Sabatier University, Toulouse.
1985 : Master 2 of Microbiology (DEA), Paul Sabatier University, Toulouse.
1984 : Master 1 of Biochemistry (maîtrise), Paul Sabatier University, Toulouse.
2005- : Position of Research Director 1st class in INSERM.
2004-2010 : Interface contract with the Toulouse University Hospital Center.
1998-2005 : Position of Research Director 2nd class in INSERM.
1993-98 : Position of « Chargée de Recherche » 1st class in INSERM
1989-93: Position of « Chargée de Recherche » 2nd class in INSERM.
Domains : gene expression, translation, angiogenesis, cancer, cardiovascular, gene transfer,
2009 Prix de la Mairie de Toulouse "les Lauriers de la Recherche"
2003 Prize of the « Concours régional de l’Innovation en Midi-Pyrénées »
2001 Medal of Knight of the « Ordre National du Mérite ».
2000 INSERM Prize of Therapeutic Research.
1986 Prize of Toulouse city: laureate of the University Paul Sabatier.
2011- : Director of the University Laboratory TRADGENE, EA 4554.
2007-2010 : Deputy Director of the "Institut de Médecine Moléculaire de Rangueil", Inserm U858.
1994-2010 : Group Leader of an Inserm Research team.
2006-08 : Director of the Federative Institute of Research 31 (IFR31), in Toulouse (France).
2004-07 : Co-founder of a Master 2P of vectorology, gene therapy and vaccination (UPS, Toulouse).
2004-05 : Coordinator of the multidiscipline program of gene and cell therapy in Midi-Pyrenees.
2003-06: Director of Inserm Unit 589 (Hormones, Growth factors and vascular pathophysiology).
2001-07 : Scientific Adviser of the General Director of INSERM for Endocrinology.
2001- : Vice-president of the Scientific Council of the Biotherapy laboratory of the Federative Research Institute Louis Bugnard (Toulouse Rangueil).
2000-2003 : Coordinator of the FP5 european consortium CONTEXTH (« New systems for controlled expression of therapeutic substances ».
11 contracts since 2005 (ANR, 2 INCA, Cancéropole GSO, ARC, Ligue Contre le Cancer, AFM, Fondation de l'Avenir, Région Midi-Pyrénées). Total 765 k€ funded.
54 total publications on pubmed, 3097 total citations (2786 without self citations), average citations per item = 44,24; factor H = 27. 16 invited conferences. 2 patents.
The team focuses onto mechanisms controlling gene expression at the translational level. In particular, we are interested in translation controlled by IRESs (internal ribosome entry sites), structural elements present in non-coding regions of mRNAs which allow translation to occur in conditions when global translation is blocked. This occurs during stress such as hypoxia or during myoblast differentiation. Our study is performed on the mRNAs of FGF1 and -2 (fibroblast growth factor 1 and 2), as these growth factors are main activators of angiogenesis, as well as myogenesis as regards FGF1. FGF1 and FGF2 mRNAs both contains IRESs. For several years our project has aimed to characterize IRESs and IRES trans-acting factors (ITAFs) that control IRES-dependent translation in various pathophysiological conditions including tumoral angiogenesis, hypoxia, skin or leg ischemia, myoblast differentiation and muscle fiber regeneration.
In addition, we have developed an approach of gene therapy of cancer by anti-angiogenesis, and of lower limb ischemia by pro-angiogenesis. This latter disease is a vascular pathology presently incurable but amputation, corresponding to a worse consequence of atherosclerosis which particularly affects diabetics. We have developed IRES-based antiangiogenic vectors able to block pancreas adenocarcinoma in animal models, and proangiogenic vectors that generate therapeutic angiogenesis in the limb, following gene transfer in mouse leg muscle. The originality of our project is to develop a combined gene therapy by using IRESs to develop multicistronic vectors for gene transfer (plasmids, AAVs and lentivectors), as the presence of IRESs in the vectors allow simultaneous expression of several therapeutic molecules.
Our present project mainly focuses on cardiovascular diseases. Very recently, we have started a programme of gene therapy of heart ischemia, based on our data on lower limb ischemia. The objective is double: on the one hand we wish to still optimize gene transfer in skeletal and heart muscle by using vector elements discovered in our basic research data, on the other hand we plan to bring in clinical assay the vectors validated in mouse, in the purpose of healing lower limb ischemia, as well as heart ischemia, in the frame of a "translational research hospital project" (CHRT) with the vascular surgery department of the University hospital of Toulouse, and in collaboration with the Biotherapy Clinical Investigation Center of Toulouse.