CV Science

OLIVIER CUVILLIER PhD Biochemistry

Course and current status

Education

University of Lille, France

1990-1994 Ph.D in Biochemistry 

Postdoctoral Training

Georgetown University, Washington, DC, USA

1995-1999 Postdoctoral Fellow

Research topics: sphingolipid metabolism, signal transduction and apoptosis

Supervisor: Prof. Sarah Spiegel

Inserm U466, CHU Rangueil, Toulouse, France

1999-2001 Postdoctoral Fellow

Research topics: sphingolipid metabolism, signal transduction and apoptosis

Director: Prof. Robert Salvayre

Professional Appointments

2005-present Head, Sphingolipids & Cancer Research Laboratory

Research topics: sphingolipid metabolism, signal transduction, angiogenesis, hypoxia, prostate cancer, kidney cancer, bone metastasis, chemoprevention

Institut de Pharmacologie et Biologie Structurale, CNRS UMR 5089, Toulouse

Director: Dr Jean-Philippe Girard

Scientific summary

Sphingolipids are a family of compounds that play, in addition to being structural constituents of cell membranes, key roles as signaling molecules. In particular, two of these sphingolipid metabolites, ceramide and sphingosine 1-phosphate (S1P) have garnered considerable attention over the last decade as critical mediators of cell death or survival. Ceramide, the central molecule in sphingolipid metabolism, mediates apoptosis whereas S1P promotes proliferation, migration, angiogenesis and cell survival . The opposing directions of ceramide- and S1P-mediated signaling gave birth to the concept of a "ceramide/S1P biostat", and the postulate that the ratio between these two lipids could determine the cell fate (Cuvillier et al, Nature, 1996).

Over the last years, our Lab has been studying the role of S1P metabolism in chemo- and radioresistance, in bone metastasis, in hypoxia signaling and in chemoprevention.

We have established that the Cer/S1P balance governed by the sphingosine kinase-1 isoform could be considered as "a sensor" of sensitivity/resistance in cancer therapies in vitro and in vivo (Pchejetski et al, Cancer Res., 2005). Targeted strategies against sphingosine kinase-1 were shown to overcome chemoresistance (Bonhoure et al., Leukemia, 2006; Bonhoure et al., Leukemia, 2008) or sensitize to chemotherapies (Pchejetski et al., Mol Cancer Ther., 2008) or irradiation (Pchejetski et al., Cancer Res., 2010) in cellular and animal models notably in prostate cancer.

We have also shown for the first time that sphingosine kinase-1 was a key regulator for the adaptation of cancer cells under hypoxic conditions in multiple lineages (Ader et al., Cancer Res., 2008) suggesting that selective inhibition of the SphK1/S1P signaling pathway could represent a pertinent strategy to control tumor hypoxia and its molecular consequences including neoangiogenesis (Ader et al., Cancer Res., 2009).

The SphK1/S1P signaling - which is upregulated in prostate cancer patients (Malavaud et al., Eur J Cancer, 2010) - can also represent a target for chemopreventive approaches using polyphenolic compounds or natural extracts in prostate cancer (Brizuela et al., Faseb J., 2010).This cancer represents an excellent candidate disease for chemoprevention, as it is typically diagnosed in elderly men. Even a modest delay in the neoplastic development achieved through pharmacological or therapeutic intervention could result in substantial reduction in the incidence of the clinically detectable disease. 

Current studies include further understanding of the role of the S1P metabolism in cell cycle, hypoxia, neoangiogenesis and metastasis dissemination and clinical studies to evaluate the potential role of S1P as a biomarker in various cancers.

More information can be found at : http://isphingo.com