1988 : DEA Biologie-Santé. Université de Bordeaux 2. Laboratoire de Physiologie Végétale, INRA, dir. : Dr. A. Pradet « Construction et utilisation d’une banque d’ADN génomique de riz permettant le clonage de gènes impliqués dans la réponse de l’embryon au stress anoxique ».
1992 : Doctorat de Sciences Biologiques et Médicales. Université de Bordeaux 2. Laboratoire de Rétrovirologie, INSERM U328, dir. : Dr. B. Guillemain « Etude de la protéase du rétrovirus HTLV-1 : production, activité vis-à-vis d’un substrat polyprotéique recombinant »
2005 : Habilitation à Diriger les Recherches. Université de Bordeaux 1. Laboratoire des Mécanismes Moléculaires de l’Angiogenèse, dir : Pr. A. Bikfalvi « Vers l’identification de nouveaux régulateurs de la croissance des tumeurs vascularisées »
1992-1995 : MRC Human Genetics Unit, Edinburgh, UK, dir. : Dr. I.J. Jackson "Retinal pigment epithelium implication during eye development"; "Mapping around the brown locus"
1995-1996 : Assistanat Hospitalo-Universitaire, Centre de Procréation Médicalement Assistée et Laboratoire de Biologie Cellulaire, CHU de Bordeaux, Université Victor Ségalen, dir. : Prs G. Mayer, C. Mathieu, J-Y. Daniel.
1996 Recruited Assistant Professor Université Bordeaux1
2007 Professorship and additional responsabilities: Organization of Genetic Program (Level year 1 to year 3); Head of 2nd year for students enrolled in Life Sciences studies; Head of 3rd year for students enrolled in Molecular and Cellular Biology studies; Head of Biology studies for international selective courses
2011 Elected Member of the National Council of Universities (section 65)
2012 Elected Member of the Scientific Council of University, Bordeaux 1
ANGIOGENESIS, EMBRYOGENESIS, ENDOTHELIUM, GENES, GLIOMA, TUMOR
Since 2001, my main research has aimed at identifying new actors of angiogenesis. New models have been designed ( eg Hagedorn et al., 2005) allowing the identification of key tumor genes regulated during the angiogenic switch, which were further investigated for their functional implication in tumorigenesis, tumor angiogenesis and patient survival.
1) FBXW7/hCDC4, an F-Box protein gene identified as downregulated in glioblastoma, was shown to control glioma cell proliferation in vitro and to be a prognostic marker for survival in glioblastoma patients (Hagedorn et al. 2007).
2) RNA interference directed against VEGF not only impaired tumor growth in the CAM experimental glioma but also induced the overexpression of CHI3L2, IL1B, PI3/elaﬁn and CHI3L1 encoding YKL-40, that were shown to be markers of bad prognosis and may be envisionned as new therapeutic targets (Saidi et al. 2008). These results indicated that anti-angiogenesis drives expression of critical genes which may relate to disease aggressiveness in glioblastoma patients under anti-VEGF therapy.
3) We showed that a combination of IL6 and VEGF inhibitors brings synergistic antitumoral benefit and reduces global activity of major pathways of cell survival, proliferation and invasiveness in remaining tumor cells that are induced after using VEGF or IL6 inhibitors alone (Saidi et al. 2009). Since then, Actemra (a humanized anti-IL6R antibody approved for use in the clinic) was evaluated alone or combined with Avastin. We show that the use of both drugs together is significantly more efficient at inhibiting tumor development than Avastin alone. The combination should now be tested in patients with fatal prognosis. This work, supported by Roche, will be submitted for publication shortly.
4) We also investigated physiological angiogenesis in the developing chick chorioallantoic membrane (CAM) using pan genomic microarrays (Javerzat et al. 2009). This study identified a restricted number of novel genes enriched in the endothelium of different species and tissues, which may play crucial roles in normal and pathological angiogenesis. To address this question, I designed a new thesis project entitled «Expression of new endothelial genes in human tumors: towards clinical correlations and therapeutical targets» (Thesis started in 2010 by V. Godard, director: S. Javerzat).
5) To investigate genes regulated by vascular endothelial growth factor (VEGF) in vivo, recombinant human VEGF was applied on the surface of the CAM and angiogenic tissue was analysed by gene profiling. Five genes encoding members of a unique family of proteins were amongst the strongest regulated genes and some of these have been studied extensively in vitro, ex vivo and in vivo (Exertier et al. in revision). More functional studies are underway to elucidate the role of several of candidates in angiogenesis.
I now focus on the challenging case of Glioblastoma, a set of tumors that develop remarkable abilities to evade anti-angiogenic therapy. I design new models to mimic these properties in vivo and ask whether combined targeting therapy can efficiently control evasive resistance.