The CNRS UMR 8104 located at the Cochin Institute (http://www.cochin.inserm.fr) in Paris
wishes to host an ATIP team in 2006.
This team will be attached to the Hematology department.
Besides access to the common facilities, a surface of at least 50 m2 will be allocated to the new
team.
Research projects developed in the hematology department:
The hematopoietic stem cells (HSCs) are multipotent cells able to generate all blood cells. The HSCs,
present in the blood or bone marrow, are used for therapeutic issues in several human diseases. They are
capable of self-renewal and/or engagement in various differentiation pathways. While differentiating, the
stem cells lose their multipotency and gain the properties of circulating blood cells.
The different research teams of the Hematology department have complementary projects aiming at
deciphering the cellular and molecular mechanisms responsible for stem cell proliferation and
differentiation. Some groups study the hematopoietic stem cell survival and expansion processes. Others
are interested in the hematopoietic progenitors already engaged in various pathways of maturing cells
such as the erythrocytic, megakaryocytic and lymphoid lineages.
The different research subjects currently developed in the Hematology department are related to:
- the development of new methods allowing HSC expansion,
- the study of the trans-differentiation potential of HSCs,
- the characterization of the role of transcription factors in the self-renewal of HSCs or in their commitment
to a specific differentiation pathway,
- the determination of the role of chromatin organization in HSC biology,
- the determination of the role of cytokines and their receptors on the behavior of HSCs and progenitors of
the different hematopoietic lineages,
- the characterization of the signaling pathways activated in response to the different cytokines, to explore
the role of signaling proteins on transcription factors involved in these differentiation processes.
The Hematology department is also currently studying the physiopathology of several human diseases,
such as:
- diseases with abnormalities of platelet formation and function,
- HIV infection where platelets could play a role in host defense,
- myelodysplastic syndromes associated to dyserythropoiesis,
- human acute leukemias related to the activation of oncogenic transcription factors,
- human acute myeloid leukemias with the study of constitutive activation of signaling pathways in primary
leukemic cells isolated from bone marrow,
- research on human leukemic stem cells after graft in recipient NOD-SCID mice
These projects are conducted with the clinical and biological hematology teams of the Cochin hospital and
also in collaboration with external hematology departments.
Several important scientific results have been recently published by the department:
1) In the area of hematopoietic stem cells (HSC), we showed that:
(i)
ex vivo expansion of HSC by passive transfer of the HOXB4 homeoprotein was possible with
maintenance of the stem cell phenotypic and genomic characteristics,
(ii)
Pitx2 homeogene expression in stromal cells is required for the onset of hematopoiesis,
(iii)
STAT5 transcription factor is necessary when the stem cells begin to cycle,
(iv)
TAL-1 transcription factor favors the erythroid differentiation and increases the HSC
compartment whereas Lnk adaptor has a negative role on HSC proliferation,
(v)
ETO2 repressor factor permits cell differentiation towards erythropoiesis and leads to
activation of Gfi-1B and p21 genes,
(vi)
IEX-1 is a new target of MAP-kinases, whose expression is regulated by the Thrombopoietin
via ERK-dependent the phosphorylation of AML1,
(vii)
B56 sub-unit of PP2A phosphatase is responsible for ERK dephosphorylation, while IEX-1
does the opposite.
2) In the area of the hematopoiesis regulation:
(i)
we determined the relationships between signaling induced by erythropoietin and GATA-1 and
TAL-1 activity,
(ii)
(iii)
(iv)
(v)
(vi)
we identified news molecules able to regulate TAL-1 properties during erythroid differentiation,
we identified the epigenetic modifications of NFE2,
we characterized the role of Vav adaptor molecule in transcriptional complexes during
lymphopoiesis,
we identified the repressive role of RelA on RelB after TNF- stimulation,
we studied the mechanisms of internalization and degradation of the Epo receptor in response
to Epo.
3) In the area of human disorders:
(i)
we showed that apoptosis of erythroid progenitors in myelodysplastic syndromes is due to Fas
and Fas ligand overexpression; a dominant negative construct of FADD is able to restore
normal erythropoiesis,
(ii)
we demonstrated the activation of the PI-3-kinase p110 delta sub-unit and its role for
proliferation in acute myeloid leukemic cells,
(iii)
we studied diseases with qualitative defect of platelets, such as the grey platelet syndrome
and the Paris-Trousseau thrombocytopenia.
(iv)
finally, we developed a model of gene therapy for hemophilia associated to facteur IX
deficiency.
The hematology department welcomes each year several students and people from the department are
involved in different teaching courses given inside Paris 5 and Paris 7 universities.
During 2006, 13 post-doc, 16 students in thesis and 9 students from masters 1 and 2 are welcomed in the
department.
Several research groups in the department belong to research networks and are financed by ARC, AFM
and/or Ligue Nationale contre le Cancer. Some groups are also financed by Cancéropole Ile de France,
and others recently gained ANR contracts.
The Hematology department in composed of 8 research teams, among a total of more than 45 teams in
the whole Cochin Institute.
Our institute also comprises excellent technological platforms such as imaging, flow cytometry,
sequencing, proteomics, anatomo-pathology, etc.
Contact :
Pr Axel Kahn
Director of the Institut Cochin
22 rue Méchain
75014 Paris
Tel. 33 1 40 51 64 57
Fax 33 1 40 51 64 73
Email : kahn@cochin.inserm.fr