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My research focuses on mammalian iron homeostasis , particularly in the key processes of heme iron storage and recycling from aged or damaged red blood cells by macrophages. I currently develop research around erythrophagocytosis, haemolysis and haem iron in brain stroke in healthy or diabetic patients.
Involved during several years as a whistleblower in a major misconduct research case in my scientific domain of expertise, I followed differents courses and I used my personnal experience and knowledge to developp actions in research integrity. LINKS         |
MINI CV
EDUCATION
- 2006: National Diploma of Habilitation to Direct Research (HDR) in Life science and Health , University Paris VII
- 1991/96 : Ph.D. in Molecular and Cellular Biology, ULP, Strasbourg, France
- 1989/90 : Master's degree in Molecular and Cellular Biology, ULP, Strasbourg, France
- 1986/89 : Bachelor of Science in Cellular Biology and Physiology, ULP, Strasbourg, France
- 2024- Today: Senior Scientist (CRHC) INSERM, U1188, DéTROI, Saint-Pierre, La Réunion, France
- 2021- 2024: Senior Scientist (CRHC) INSERM, U1220, IRSD, Toulouse, France
- 2016-2021: Senior Scientist (CRCN) INSERM, U1220, IRSD, Toulouse, France
- 2011-2016 : Senior Scientist (CR1) INSERM, U1043, CPTP, Toulouse, France
- 2007-2010 : Senior Scientist (CR1) INSERM, UPR2301, CNRS, ICSN, Gif-Sur-Yvette, France
- 2006-2007: Senior Scientist (CR1) INSERM, U773, Faculté Xavier Bichat, Paris, France
- 2005-2006: Senior Scientist (CR2) INSERM, U656, Faculté Xavier Bichat, Paris, France
- 2002-2005: Senior Scientist (CR2) INSERM, U409, Faculté Xavier Bichat, Paris, France
- 1997/2002: Post-doctoral research in the laboratory of Professor Philippe Gros, Department of Biochemistry, University McGill, Quebec, Canada.
RESEARCH SUPPORT EXPERIENCE
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Scientific communication : Conceptor -designer and administrator (Webmaster) of the Inserm 1220 and Inserm 1188 websites, computer graphics work with creation of images, diagrams and logo
Scientific animation : Commitee leader organisation of seminars and progress report , scientific retreat, and other events... Ecoresponsability : Commitee leader Sensibilisation and action (paper recycling, energy economy, ecomobility) Secretary of the actual Macrophage club (National organisation) Creation of The Macrophage club in Toulouse and Occitania (2016) Webmaster & Organization of symposia & workshop |
Scientific integrity and good practice in research
Having been involved for several years as a whistleblower in a major case of research misconduct in my scientific field, I followed an INSERM training course and used my experience and knowledge to develop this major and important mission in support of Research and Science . My goal is to help people, both new and experienced researchers, to be aware and to learn about all aspects of research misconduct and good practices in research. I do this by creating easy-to-understand documents, offering courses 'Master and PhD student) and giving seminars. My aim is to make sure everyone in the scientific community understands how important it is to do research ethically with good practices and avoids mistakes that could be around any scientist. As a support, I designed a website all about research integrity. |
SCIENTIFIC EXPERTISE
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Animal and Cellular models:
Techniques and Methods:
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*NOTE : Major expertice : Purification, characterization and use of polyclonal antibodies against iron transporters. The affinity purification of the various custom antibodies obtained in rabbits requires the production and purification of recombinant proteins in E. coli used for the specific retention and elution of the antibodies present in rabbit serum (affinity column). As part of this program, I supervised several students and members of my team to carried out the purification of several antibodies directed against different murine and human iron transporters. These tools and their use, allowed me to acquire an international recognized expertise in the detection of iron transporters ex vivo in cell culture and in vivo in mice (expression and localization analysis; western blot, immunofluorescence, electron microscopy ...). Many research groups encounter difficulties in finding specific antibodies in the trade and having neither the means nor the expertise to develop them. So they contact me to request certain antibodies needed for their studies as well as my expertise in acquisition (protocols) and analysis of the detection of iron transporters (collaboration in the form of a Material Transfer Agreement MTA). |
Research interest:
MACROPHAGE IRON METABOLISM AND PATHOLOGIES.
Since my post-doc in McGill university, my research focuses on mammalian iron homeostasis and in particular in the key processes of heme iron storage and recycling from aged or damaged red blood cells by macrophages. For this purpose I developed a physiological model that mimics the process of erythrophagocytosis including red blood cells ageing, recognition and engulfment by macrophages. Using this model, we studied the different steps of heme iron recycling by macrophages①. We clarified important regulation at both mRNA and protein levels of Ferroportin (FPN), the only mammalian iron exporter identified to date. We also showed that Hepcidin (HAMP), a small peptide considered as the major hormonal regulator of iron homeostasis, induces a rapid internalization and degradation of the macrophage iron exporter present at the cell surface of macrophages. To get insight into the molecular mechanisms involved in HAMP mediated downregulation of FPN protein, we developed cellular and proteomic approaches to better define the environment of FPN in macrophage cellular membranes②. We also studied the relation between macrophage iron recycling, infection with intracellular pathogens (such as salmonella) and anemia of inflammation③.
I am also interested in the implication of red blood cells and macrophagic iron in Atherogenesis (Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis. & Iron gene expression profile in atherogenic Mox macrophages.).
Since my post-doc in McGill university, my research focuses on mammalian iron homeostasis and in particular in the key processes of heme iron storage and recycling from aged or damaged red blood cells by macrophages. For this purpose I developed a physiological model that mimics the process of erythrophagocytosis including red blood cells ageing, recognition and engulfment by macrophages. Using this model, we studied the different steps of heme iron recycling by macrophages①. We clarified important regulation at both mRNA and protein levels of Ferroportin (FPN), the only mammalian iron exporter identified to date. We also showed that Hepcidin (HAMP), a small peptide considered as the major hormonal regulator of iron homeostasis, induces a rapid internalization and degradation of the macrophage iron exporter present at the cell surface of macrophages. To get insight into the molecular mechanisms involved in HAMP mediated downregulation of FPN protein, we developed cellular and proteomic approaches to better define the environment of FPN in macrophage cellular membranes②. We also studied the relation between macrophage iron recycling, infection with intracellular pathogens (such as salmonella) and anemia of inflammation③.
I am also interested in the implication of red blood cells and macrophagic iron in Atherogenesis (Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis. & Iron gene expression profile in atherogenic Mox macrophages.).
Specific aims:
I have joined the Unit of Détroi (Inserm UMR1188) in order to share my expertise and to develop research in erythrophagocytosis, haemolysis and haem iron in stroke. This research will enable us to gain a deeper understanding of the implications and consequences of these processes for brain cells.
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Diagram of vascular and erythrocyte complications in ischaemic stroke (A), haemorrhagic stroke (B) and microhaemorrhage (C). In these 3 cases, RBCs appear to be involved in these pathologies via the release of degradation products (notably Hb/haem/iron) which cross the blood-brain barrier (A and C) or via their infiltration into nervous tissue (B). In haemorrhagic stroke (B), RBCs can be phagocytosed by microglia and macrophagic cells derived from circulating monocytes. The involvement of neurons, oligodendrocytes, astrocytes and endothelial cells in the elimination of infiltrated RBCs is poorly described. It has been suggested that during microhaemorrhages (C), brain endothelial cells may have erythrophagocytosis activity (16). Legend. (1): RBC; (2): Altered or senescent RBC; (3): Haemolytic RBC; (4): Circulating monocyte; (5): Thrombus; (6): Lipid deposits; (7) Endothelial cell; (8): Pericytes; (9): Astrocytes; (10): Neurons; (11): Oligodendrocytes; (12): Microglia; (13): Infiltrating monocyte; (14): Monocyte-derived macrophage; (15) Haemoglobin; (16): Iron molecules.
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WORKING HYPOTHESIS
Red blood cells appear to play an important role in the progression of cerebrovascular pathologies, but their involvement is still poorly understood. It is therefore important to better define the pathophysiological consequences of the extravasion of these cells into nervous tissue. Our project will attempt to study the interactions and fate (binding, erythrophagocytosis and haemolysis) of normal or altered RBCs (by erythptosis or glycation under hyperglycaemic conditions (mimicking diabetes)) and their derivatives (Hb/hem/iron) on the cellular activity and death (ferroptosis and others) of brain cells (glia and neurons).