Team description

Keywords: Paracrine signaling, non-oncogene addiction, angiogenesis

On the ground of our interests for molecular piracy exerted by tumor cells to survive, adapt and remodel their environment, we explore the signaling mechanisms involved in non-oncogene addiction and loss of vascular homeostasis.

Main Projects:

1. Vascular Permeability in tumors.

The endothelial barrier tightly regulates the exchange of fluids, cells and nutrients between the blood compartment and the surrounding tissues. Within the tumor microenvironment, the integrity of the vascular wall is compromised and drives many features of the tumor vasculature, such as poor perfusion, perivascular inflammation, increase in interstitial fluid pressure and edema. We are exploring the signaling mechanisms involved in the loss of barrier integrity. We identified several tumor-secreted factors operating in a paracrine fashion, free in the medium and/or transported through extracellular vesicles.

2. NF-kappaB activating signalosomes in lymphocytes and lymphoma.

To survive and proliferate, the activated B-cell like (ABC) subtype of diffuse large B-Cell lymphoma (DLBCL) exploits a multi-protein complex that contains CARMA1, BCL10 and MALT1 (CBM complex) normally engaged in conveying NF-kappaB following antigen receptors engagement. We are deploying proteomic and genetic screens to characterize the CBM interactome in lymphocytes and lymphoma cells. Because reversible ubiquitylation processes ensure NF-kappaB activity, a special emphasis is placed on E3-ligases and deubiquitylases (DUBs).

3. Tumor vascular niche in brain tumors.

Glioblastoma-initiating cells, also known as stem-like cancer cells have been found in the vicinity of brain endothelial cells, suggesting that functional interactions take place in the vascular niche. A great deal of attention has been given to these tumor cells because they are believed to be responsible for tumor initiation, radio- and chemo-resistance, and recurrence. We are studying the molecular basis of this crosstalk in vitro and in vivo. In particular, we found that brain endothelial cell secrete factors that provide positive signals to maintain glioblastoma-initiating cell properties.

4. Multi-proteins complexes and dynamics in lymphocytes.

Innate and adaptive immunity engage NF-kappaB transcription factors via reversible ubiquitylation of context-specific adaptors. However, how apical ubiquitylated molecules mediate the activation of cytosolic NF-kappaB continue to be elucidated. We are interested in defining the composition and the modulation of these large signalosomes following the engagement of antigen receptors.

Expertises / technical competence

Expertises

Paracrine signaling, extracellular vesicles, angiogenesis, brain tumors, lymphoma, cell death, cell adhesion, endothelium

Technical competence

• Characterization of extracellular vesicles
• ubiquitination and post-translational modification
• orthotopic xenografts
• vascular permeability

Collaborations

National Collaborations

H Enslen, Institut Cochin

Paris T Galli, Centre de Psychiatrie & Neurosciences, Paris

J Goetz, Inserm, Strasbourg H Gronemeyer, IGBMC, Strasbourg

C Hivroz, Institut Curie, Paris

G Pages, IRCAN, Nice

D Ricard, Hôpital d’Instructions des Armées, Percy

International Collaborations

RC Glen, Cambridge, UK

MJ Lenardo, NIH, USA

F Sanchez, Valdivia, Chile

Institut de Recherche en Santé de l'Université de Nantes

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