Scientific topics
Keywords
ITMO
Anne-Catherine Prats PhD Molecular Virology
Course and current status
- Present position:
Group leader, Research Director in Inserm
Laboratory:Team LYMPHACTOR Garmy-Susini/Prats « Molecular regulations of lymphangiogenic factors in cardiovascular pathologies", Inserm UMR1297, Institut des Maladies Métaboliques et Cardiovasculaires I2MC (Dir D. Langin), Toulouse
- Previous laboratories :
2011-2015 : TRADGENE EA4554 « Translational control and gene therapy of vascular diseases » (Dir AC Prats), Institut des Maladies Métaboliques et Cardiovasculaires I2MC , 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
Ø Diplomas
1994 : HDR (Enabling to Direct Research), University Toulouse III Paul Sabatier.
1988 : Doctorate thesis in Molecular Virology (PhD), University Toulouse III Paul Sabatier.
1985 : Master 2 of Microbiology (DEA), University Toulouse III Paul Sabatier.
1984 : Master 1 of Biochemistry (maîtrise), University Toulouse III Paul Sabatier.
Ø Scientific career
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.
Ø Domains of expertise and consultance
Domains : gene expression, translation, RNA, angiogenesis, cancer, cardiovascular, gene transfer, gene therapy
- Prizes, awards
2015 Medal of "Chevalier de la Légion d'Honneur".
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 "Chevalier de l'Ordre National du Mérite".
2000 INSERM Prize of Therapeutic Research.
1986 Prize of Toulouse city: laureate of the University Toulouse III Paul Sabatier.
- Main functions
2016- : Group Leader of Inserm Team LYMPHACTOR Garmy-Susini/Prats at I2MC, Inserm UMR1297, labeled by the "Fondation pour la Recherche Médicale".
2022- : Member of the Ligue Nationale Contre le Cancer scientific committee
2022- : President of the FNRS Committee SVS-1 (Sciences of Life and Health), Brussels
2005- : Responsible of teaching units of vectorology and gene therapy in the Master 2 of vectorology, gene therapy and vaccination and the Master 2 of pathophysiology (University Toulouse III). Co-responsable of the Master 2 of vectorology since 2023.
2019- : Reviewer Editor at IJMS (International Journal of Molecular Science)
2020-21 : Referee at the FNRS Committee SVS-1 (Sciences of Life and Health), Brussels
2018-2022 : Coordinator of the RIBOCARD consortium (ANR)
2016-21 : Member of the Executive Board of the Federal University of Toulouse
2015-20 : Adviser at the Scientific and Academic Councils of University Toulouse III Paul Sabatier.
2011- 2015 : 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.
2001-2010 : Vice-president of the Scientific Council of the Biotherapy laboratory of the Federative Research Institute Louis Bugnard (Toulouse Rangueil).
2006-08 : Director of the Federative Institute of Research 31 (IFR31), in Toulouse (France).
2001-07 : Scientific Adviser of the General Director of INSERM for Endocrinology.
2004-07 : Co-founder of a Master 2P of vectorology, gene therapy and vaccination (UPS, Toulouse).
2003-06: Director of Inserm Unit 589 (Hormones, Growth factors and vascular pathophysiology).
2004-05 : Coordinator of the multidiscipline program of gene and cell therapy in Midi-Pyrenees.
2000-2003 : Coordinator of the FP5 european consortium CONTEXTH (« New systems for controlled expression of therapeutic substances ».
- Contracts
16 contracts since 2005 (ANR, 2 INCA, Cancéropole GSO, ARC, Ligue Contre le Cancer, AFM, Fondation de l'Avenir, Région Midi-Pyrénées, FRM). Total 2 M€ funded.
Partner of european projects THERALYMPH (gene therapy of lymphedema) and CARDIOPATCH (gene therapy of heart failure)
- Scientific production
80 total publications on pubmed (Prats AC or Burger AC), 5191 total citations, average citations per item = 58,33; factor H = 38. 21 invited conferences. 2 patents. ORCID 0000-0002-5282-3776
Recent marking publication:
Scientific summary
My research project focuses onto mechanisms controlling gene expression at the translational level in cancer and ischemic diseases. In particular, I have been interested for several years in the regulation of translation by IRESs (internal ribosome entry sites), structural elements present in non-coding regions of mRNAs, which allow protein synthesis to occur in stress conditions when global translation is blocked. This happens in the center of tumors or in ischemic tissues where cells are submitted to hypoxia. We have focused onto angiogenic and lymphangiogenic factors, in particular fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) families, that are expressed in response to hypoxia. We have identified IRESs in the mRNAs of several FGFs and VEGFs and shown that these IRESs allow translational induction of these factors during hypoxia in tumors, as well as in ischemic heart and hypoxic cardiomyocytes. In cardiomyocytes, a high flow PCR array has demonstrated that that, unexpectedly, most growth factors are not induced in the transcriptome, but are induced in the translatome, indicating a crucial role of translational control to stimulate angiogenesis and lymphangiogenesis in ischemic heart.
Furthermore, we have identified several IRES trans-acting factors, including nucleolin, p54nrb, hnRNPM and vasohibin-1, that are involved in this translational induction in response to stress. Interestingly, IRESs from different mRNA groups are sequentially activated during hypoxia, leading us to propose the concept of IRES regulons governing the translational induction of families of mRNAs. IRESome composition is under investigation in the purpose of understanding the molecular mechanisms of IRES activation by hypoxic stress. Presently, I am coordinating the consortium RIBOCARD (financed by ANR) to search for specialized ribosomes (with rRNA or ribosomal protein modifications) responsible for IRES-dependent translation in stress cardiomyocytes.
Recently, we have discovered that the long non-coding RNA NEAT1 is the key regulator of IRES-dependent translation during hypoxia. This RNA is present in a nuclear body, the paraspeckle, that appears in stress conditions. We show that the paraspeckle is an assembly platform of the IRESsome, the nucleoprotein complex responsible for ribosome internal entry. Thus IRES-dependent translation, although occuring in the cytoplasm, has a nuclear story regulated by Neat1 in the paraspeckle.
We are also involved in translational research by developing an approach of combined gene therapy using IRES-based vectors (plasmids, lentivectors or AAVs). The presence of IRESs in vectors allow expression of several genes of interest from a single mRNA. We have validated this strategy on animal models of pancreas adenocarcinoma (anti-angiogenesis) and ischemic leg (angiogenesis). In both cases the combination of two therapeutic molecules has a synergistic effect on therapeutic benefit and allow to use molecules at lower doses, thus preventing side effects of treatment.
This translational research project is presently focused onto ischemic heart disease and secondary lymphedema.
Heart failure remains a public health issue for which combined gene therapy may provide a solution by generating more efficient treatments. We have designed a tricistronic lentivector co-expressing an angiogenic factor (FGF2), an anti-fibrotic factor (apelin) and a stimulator of heart contractile function (SERCA2a), aimed to simultaneously restore three parameters of heart failure. This lentivector, injected by intracardiac administration into infarcted mouse myocard, generates a stronger therapeutic benefit on cardiac function than lentivectors expressing one or two of these molecules. Furthermore, a high flow PCR array shows that the triple treatment acts by restoring the gene regulation networks in ischemic heart. We are presently developing a clinical assay project from these data, obtained in the frame of a "translational research hospital project" (CHRT), with the cardiology department of Toulouse hospital (Pr Jérome Roncalli) and the Biotherapy Clinical Investigation Center of Toulouse.
As regards lymphedema, it results from lymphatic dysfunction occuring in particular (considering the secondary lymphedema) after lymph node ressection and cancer chimiotherapies. We have recently developed a combined RNA therapy able to treat lymphedema successfully in a mouse model. A clinical assay will be launched soon.
I am presently a partner of two european programs for gene therapy: THERALYMPH (coordinated by B. Garmy-Susini in our team) and CARDIOPATCH (coordinated by F. Prosper, Universidad de Navarra)
