Isabelle MARIDONNEAU-PARINI PhD
Course and current status
Director of Research Inserm
Group leader “Differentiation and Activation of Phagocytes”
Laboratory
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089/ Université Toulouse III , 205 route de Narbonne, 31077 Toulouse cedex 04
Tel : 33- (0)5 61 17 54 58
e-mail : maridono@ipbs.fr
Diploma
PhD from University of Paris VI
Doctorate in Molecular and Cellular Pharmacology, University of Paris VI
Positions
Scientific Research
1980 PhD, Necker Hospital, University Paris V, Paris, France
1983-84 Post-doctoral position, European Science Foundation fellowship, Clinica Medica II, Università di Medicina, Pavia, Italy
1985-86 Research Associate, Boston University School of Medicine, Boston, MA, USA
1987-88 Post-doctoral positions, FRM and ARC fellowships, Pasteur Institute Paris
1988 Permanent position Chargée de Recherche INSERM, Pasteur Institute Paris.
1989 Sabbatical year Centre de Génétique Moléculaire, CNRS, Gif/Yvette, France
1990-93 Group leader Institut Cochin de Génétique Moléculaire, Paris
1994 - Group leader. CNRS UMR5089, Toulouse, France
Research evaluation
2001-03 Scientific adviser “Health-Biology” for the French Ministry of Research at the Delegation for Research and Technology in Midi-Pyrénées and expert for ANVAR Midi-Pyrénées for the National Competitive Examination for the Creation of Companies in Innovative Technology.
2003-05 Scientific adviser for the French Ministry of Research (Paris). Mission for Sciences, Technologies and Education (MSTP5). Department of Medicine, Biology, Health.
2007-09 Scientific manager at AERES. Section 2. Evaluation and consultation of research laboratories. Expert in Inflammation and host-pathogens interactions.
Scientific summary
Macrophage tissue infiltration is a hallmark of several pathological situations including cancer, neurodegenerative disorders and chronic inflammation, its control is becoming a therapeutic challenge.
We have shown that, in 3-dimensional (3D) environments, macrophages use the mesenchymal migration mode (protease-dependent) in addition to the amoeboid migration mode (protease-independent) used by all leukocytes depending on the environmental constraints. Moreover, we show that macrophage mesenchymal migration into 3D cell spheroids requires matrix metalloproteases but not into extracellular matrices. Thus macrophages are able to sense the extracellular environment, adapt their migration mode, and use different sets of proteases. Podosomes are cell structures with proteolytic activity constitutively expressed in macrophages and macrophage-derived cells. Podosomes are made of a F-actin core surrounded by integrins. During 3D migration, they either reorganize as 3D-podosomes when macrophages use the mesenchymal mode or disappear when they use the amoeboid migration. Podosome organization and proteolytic activity are regulated by the tyrosine kinase Hck which translates into a 3D mesenchymal migration defect in Hck-/- macrophages. As measured by atomic force microscopy, podosomes exhibit periodic oscillations of their rigidity under the control of acto-myosin complexes which might participate to their mechanosensing activity. Cell migration and podosome formation examined in resident, elicited, polarized macrophages and all leukocyte subtypes collected from blood, show different migration capacities among leukocytes and an additional aspect of the macrophage versatility.
The study of macrophage migration in several 3D environments is starting to shed light on molecular and cellular mechanisms involved in that process, a step towards identification of pharmacological targets.
