Education (degrees, dates universities)
Bachelor Sciences, University of Mexico (1965)
Medical Doctor, University of Mexico (1971)
Master Biological Sciences, University of Paris (1977)
Sciences Doctor, University of Paris( 1980)
Career/Employement (employers, positions and dates)
Intern in Medicine, National Nutrition Institut, Mexico City 1972 -1974
Chief Resident, National Nutrition Institut, 1974 -1976
Resident in Hematology, Hôpital Saint-Louis, Paris 1976 -1978
Fellowship in Hemostasis, Hôpital Cochin-INSERM, Paris 1979 -1981
Full time investigator, INSERM, Paris 1982 -1989
Director of Research 2nd Class, INSERM, Paris 1989-1995
Director of Research 1st Class, INSERM, Paris 1996-2012
Director of Research, Emeritus, INSERM, PARIS 2012-
(1) main field Biochemistry of Hemostasis and Fibrinolysis
(2) other fields Vascular Biology
(3) current research interests
Cell-derived microparticles and Plasminogen activation in cardio and neurovascular pathology
With my graduate students and co-workers we are pioneer in the study of fibrinolytic microvesicles (MVs) as functional messengers of plasmin generation. Since plasminogen activation is a property not only of vascular cells but also of other cell types including epithelial and inflammatory cells, our working hypothesis is that MVs derived from cells that express plasminogen activators may generate, disseminate and transfer plasmin proteolytic activity (Blood, 2007). For instance, besides endothelial cells and leucocytes, neurons are able to release microvesicles bearing plasmin and tPA activity (Biochem J 2010). We have found that endothelial cell- and leucocyte- derived microvesicles bear the machinery necessary for plasmin formation including plasminogen activators and its receptors: tPA for endothelial MVs and the uPA/uPAR system for leukocyte MVs (Haematologica 2013).
Furthermore, we have discovered a new mechanism for plasmin formation that bypass the requirement for co-assembly of plasminogen and uPA on the same surface (Blood 2010). These heterotypic cell-to-cell (platelets/ monocytes; platelets/MPs), cell-to-matrix (leukocytes/fibrin), or MPs-to-matrix (MPs/fibrin) proteolytic cross-talk represents an alternative pathway for localized plasmin formation that may be relevant to processes implicating cell migration and MP dissemination, i. e. inflammation or angiogenesis. Finally, our data provide additional evidence for a novel role of MPs and platelets, as vectors that generate and propagate plasmin fibrinolytic and/or proteolytic activity, and could thereby constitute a pharmacologic tool.
Presently, at the Inserm reaserch unit UMR_S 1140 (Faculty of pharmaceutical and biological sciences, Paris) we are studying the fibrinolytic and microvesiculation properties of human bone marrow mesenchymal stem cells as a potential tool for cell therapy in ischaemic diseases. We are also studying the role of microvesicles in fibrinolysis and NET transformation of PMN in ischaemic diseases.
Current fields of interest:
- Microvesicles as messengers and actors of fibrinolytic and proteolytic activity
- Fibrinolysis and proteolysis in inflammatory diseases
- Microvesicles, fibrinolysis and NET transformation of PMN in ischaemic disease.
- Plasminogen activation-dependent extracellular proteolytic activity in atherothrombosis