Current Position:
2001-present: Team leader Institut Cochin. Research Director (DR2, INSERM).
INSERM U1016, CRNS UMR 8104, Cochin Institute, Department of Immunology-Hematology.
Previous professional experience:
1984-1988: Ph.D. thesis in Immunology. INSERM U25, Necker Hospital. Pr. J. F. Bach. Supervisor: Dr. L. Halbwachs-Mecarelli
1989-1990: Post-doctoral position. Department of Medicine, Cornell University Medical College, New York, USA. Dr. C. F. Nathan's lab.
1990-1991: Instructor position in C. F. Nathan's lab.
1992-1993: Permanent Research position (CR2) at INSERM, U90, Necker Hospital.
1993-2001: Research position (CR1 at INSERM U363 then 567, Cochin Institute, department of Hematology.
Main interests:
Fundamental molecular mechanisms governing adult hematopoiesis. Roles of growth factors and signaling pathways in the control of hematopoietic stem cell (HSC) self-renewal, commitment, expansion and differentiation, with a particular focus on the mitogen activated protein kinase (MAPK) pathway.
Main questions asked:
a) How a signalling pathway (e.g. MAPK) is triggered and used selectively by two different growth factors receptors expressed in a given cell context? How a single receptor impacts signaling differently in two different cell contexts (HSC vs committed progenitor)?
b) What are the downstream MAPK protein substrates and target genes regulating the different, and sometimes opposite, final biological outcomes of this pathway in HSCs, committed progenitors and differentiated cells? These studies include screening of new MAPK substrates/target genes and analysis of already identified MAPK targets/substrates.
c) What is the impact of growth factor signaling on DNA repair and aging of HSCs, bone remodeling and HSC interaction with the bone marrow niche?
e) How are MAPK pathways and substrates subverted in leukemic cells? Can we find new therapeutic targets and compounds to manipulate HSCs and eradicate leukemic stem cells?
Models used:
knock-out mice, human normal and leukemic bone marrow cells, confocal microscopy imaging on FACS-sorted single cells, genomic approaches to identify the genes controlled by ERK1/2 MAPK in HSCs and biochemical proteomic approaches to discover new kinase substrates.