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Olivier Spertini
Michel Duchosal

Michel Duchosal,
MD, Professor


Research topics

Molecular characterization and treatment of haematological malignancies

Pre-clinical evaluation of a novel anti-tumor agent in hematological malignancies.
Activation of molecules leading to apoptosis originate through cell surface death receptors or from mitochondria. This latter pathway is targeted by APO 866 which inhibits specifically nicotinamide phosphoribosyltransferase (NAPRT), a key mitochondrial enzyme generating NAD. NAD depletion induces high levels of apoptosis, particularly in cancer cells. The scientific objective is to test the efficacy of APO866 alone or in combination with chemotherapeutic drugs on a panel of hematological cancers. Furthermore, the project will identify cell biomarkers as indicators of APO866 sensitivity.

Molecular characterization of post-transplantation lymphomas.
Solid organ and hematopoietic stem cell transplanted patients may suffer from (posttransplant) lymphoproliferative diseases (PTLD). PTLD development is linked to immunosuppression, and is often induced by uncontrolled growth of B cell infected by the Epstein-Barr virus (EBV). The in vivo steps leading to such lymphomas are poorly characterized.
The aim of our project is to characterize molecular signatures associated with the development of PTLD.
We are applying molecular biology techniques such as DNA microarray and RT PCR on a laboratory model of aggressive human B cell PTLD. Indeed immunodeficient mice transplanted with human lymphocytes generate such human PTLD.
The study may provide new diagnostic and prognostic tools for the management of this disease, as it has been the case in other types of lymphomas. The study may also help to design new therapeutic strategies aiming at preventing the development of or at treating overt lymphomas in the context of immunosuppression and transplantation.

Laboratory members

Nahimana Aimable PhD Aimable.nahimana@chuv.ch
Aubry Dominique Technician Dominique.Aubry@chuv.ch
Béguin Kueen-Moi Lab helper Kuen-Mooi.Beguin@chuv.ch
Menu Philippe PhD student

Selected publications

1: Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, Trumpp A.
    IFNalpha activates dormant haematopoietic stem cells in vivo.
Nature. 2009;458(7240):904-8.
2: Greaney P, Nahimana A, Lagopoulos L, Etter AL, Aubry D, Attinger A, Bassi I, Sordat B, Demotz S, Dupuis M, Duchosal MA.
    A novel Fas agonist induces high levels of apoptosis in haematological malignancies.
Leukemia Research 2006;30:415-426
3: Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, Tjørnelund J, Dawson KM, Dupuis M, Duchosal MA.
    The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies.
Blood. 2009;113(23):6035-7
4: Nahimana A, Aubry D, Butcher S, Muchosal MA.
    NAD targeting efficiently kills hematological cancer cells.
Blood 2009;113(23):6037-8



Dernière modification le 11.01.2011 - Impressum - Informations juridiques

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