|
CONTACTS
|
|
EQUIPE 4 : METABOLISME DU FER: DE LA REGULATION A LA THERAPIE
TEAM 4 : IRON METABOLISM:FROM REGULATION TO THERAPY |
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
- 2021- Présent: 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
Scientific integrity and good research practices
Involved during several years as a whistleblower in a major misconduct research case in my scientific domain of expertise, I followed an INSERM formation and I used my experience and knowledge to develop this great and important mission in research support in the name of INSERM. (Conceptor-Designer of webpage dedicated to research integrity, create awareness and educate thought documents, courses, and seminars , young and mature researchers to all aspect of misconduct research. )
OTHER RESEARCH SUPPORT EXPERIENCE
Since the creation of the IRSD in 2016, I was identified as the correspondent of several actions for the credit of IRSD members as well as local and national research community :
- Scientific communication correspondent : Conceptor -designer and administrator (Webmaster) of the Inserm 1220 website, computer graphics work with creation of images, diagrams and logo for the teams.
The website is a important communication tool with : Progress report & seminars announcement, calendars/agenda, data exchange (publication, thematic), scientific and technological watch and collaborative work (contact). The website presents the institute, its values, its objectives (global and by team), its services (administration, logistics), its services (platforms), its productions (discoveries, publication) and makes it possible to increase the visibility of the institute.
- Scientific animation correspondent (seminar and progress report organization, scientific retreat, other events...)
I led a committee at IRSD to organise both scientific and "team "building" activities in the institute in order to create a convivial atmosphere of scientific excellence .
- Sustainable development correspondent
I recently led a committee dedicated to the reflection and implementation of measures (energy saving, transport, recycling) to limit the impact on the environment of our activities.
- Creation and animation of The Macrophage club in Occitania / Organization of symposia
Scientific expertise
|
Animal and Cellular models:
Techniques and Methods:
|
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 topics
MACROPHAGE IRON METABOLISM AND PATHOLOGIES.
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 macrophagic iron in:
- Atherogenesis (Marques et al, BBA2016). Our results indicate a decrease in the export of macrophagic iron via FPN under atherogenic conditions (inflammation and oxLDL). This decrease would lead to an increase in intracellular iron in macrophages and could thus contribute to the accumulation of iron in the atheroma plaque and its destabilization.
-Sensitivity to salmonella infection (Willemetz et al, Front Immunol, 2017) via analysis of the FPN-HAMP regulatory axis. Our ex vivo (macrophage culture) and in vivo (mouse iron pathology models) results clearly demonstrate a downregulation of FPN during salmonella infection. Our work is in opposition to the literature and raise new questions on inflammatory infectious anemias and their therapies.
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 macrophagic iron in:
- Atherogenesis (Marques et al, BBA2016). Our results indicate a decrease in the export of macrophagic iron via FPN under atherogenic conditions (inflammation and oxLDL). This decrease would lead to an increase in intracellular iron in macrophages and could thus contribute to the accumulation of iron in the atheroma plaque and its destabilization.
-Sensitivity to salmonella infection (Willemetz et al, Front Immunol, 2017) via analysis of the FPN-HAMP regulatory axis. Our ex vivo (macrophage culture) and in vivo (mouse iron pathology models) results clearly demonstrate a downregulation of FPN during salmonella infection. Our work is in opposition to the literature and raise new questions on inflammatory infectious anemias and their therapies.
links |
SCIENTIFIC PRODUCTION |
pictures
phagocytes aggregation in iron overload liverImmunohistofluorescence in liver section.
|
Iron in the liverIron is visualized in histological section of the liver after a Perls Prussian Blue staining
|
