Director of Research at INSERM
LIMMS/CNRS-IIS, The University of Tokyo, Lille, France
- 1998 Habilitation, Doctoral School of Life & Health, University of Lille, Lille
- 1990 PhD, Cell & Molecular Development Biology, University of Paris VI, Paris
- 2005-… Directeur de Recherche INSERM – Tenure position
- 1994-2005 Chargé de Recherche INSERM – Tenure position
- 1994-1995 Instructor, Joint Center for Radiation Therapy – Harvard Medical School, Boston, MA, USA
- 1992-1993 Instructor, Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, USA
- 1991 Post-doctoral research fellow, Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, USA
- Member of the board of the French Angiogenesis Society
2007-2011: 1stPresident of the French Angiogenesis Society
- Member of Société Française du Cancer
- Member of the European Association for Cancer Research
- Member of the Editorial Boards of ‘Experimental Hematology and Oncology‘, ‘International Journal of Chronic Diseases‘, ‘Oncology Letters‘
- President of the Scientific committee of ‘Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), section Flandres-Artois’,
SELECTED ONGOING PROJECTS
The endothelium is the cell monolayer which lines the inner side of blood vessels in direct contact with the circulation (Figure 1, top). Endothelial cells play essential roles in the exchanges of gas and metabolites between blood and tissues, in the regulation of vascular dilation, in thrombosis, in angiogenesis, and in the immune response. Blood vessels are essential to the growth of most solid tumors since new blood vessels formed through the process of angiogenesis – the formation of new blood vessels from existing ones by a budding process – sustains a constant supply of nutriments and oxygen to the developing mass (Figure 1, bottom).
Figure 1. Top: Schematic transversal section of small (top) and large (bottom) blood vessels. Bottom: Schematic of sprouting angiogenesis, the formation of new blood vessels from existing ones
Our specific interests are focused on the characterization of the molecular mechanisms by which blood vessels endothelial cells regulate their activation toward immune cells (Figure 2). Indeed, in order to kill tumor cells, circulating immune cells must first infiltrate the tumor mass and this infiltration is limited by the blood vessel endothelium. The tumor blood vessel endothelium, although imperfectly tight, actively protects tumor cells from the immune system through its barrier function.
Figure 2. Schematic of the non-activated/activated states of the endothelium
In order to study this process, we studied the tumor blood vessel endothelium activation in vivo and assessed the role of this activation in the infiltration of immune cells within the tumor mass (Figure 3, Delfortrie et al. Cancer Res. 2011)
Figure 3. Tumor blood vessels (CD31, green) & infiltrated T-cells (CD3ε, red), nuclei (DAPI, blue)
We also reproduce in vitro the endothelial monolayer and study the adhesion of immune cells onto this resting or activated endothelium (Figure 4)
Figure 4. Adhesion of fluorescent immune cells onto endothelial cells in vitro
Since working within the SMMiL-E project, we are interested in designing blood-vessel on-chip BioMEMS in which we assess endothelial integrity and permeability and from which sprouting angiogenesis may be induced. Our BioMEMS are designed in multiwell plate format to be used for high throughput drug screening.
Elise Delannoy, an Ecole Centrale Lille engineer and currently a PhD student in SMMiL-E, successfully created 3D tubular structures within a hydrogel, lined them with human primary endothelial cells which organize themselves into perfusable lumens, display a valid endothelium integrity and respond to natural permeability stimuli.
Figure 5. Confocal imaging of an engineered vessel at SMMiL-E
The present devices allow to reproduce an initial blood vessel from which angiogenesis may be induced. The next steps are to perfuse the devices under controlled conditions and to be able to visualize the angiogenic process using real-time video microscopy. The initial vessel response to pro-inflammatory cytokines will be further validated by its ability to allow the arrest of immune cells. The device will eventually be integrated in an automated robotic platforms to perform drug screening.
We are also working on setting up new perfusion microfluidics in order to reproduce the blood circulation within our BioMEMS (Figure 6).
Figure 6. Microfluidic setup to perfuse vascular BioMEMS under real-time microscopy.
SELECTED PUBLICATIONS (2016-19)
- Usuba R, Pauty J, Soncin F, Matsunaga YT. EGFL7 regulates sprouting angiogenesis and endothelial integrity in a human blood vessel model. Biomaterials (2019) 197:305-316.
- Pauty J, Usuba R, Cheng IG, Hespel L, Takahashi H, Kato K, Kobayashi M, Nakajima H, Lee E, Yger F, Soncin F, Matsunaga YT. A Vascular Endothelial Growth Factor-Dependent Sprouting Angiogenesis Assay Based on an in Vitro Human Blood Vessel Model for the Study of Anti-Angiogenic Drugs. EBioMedicine. (2018) 27:225-236.
- Pinte S, Caetano B, Le Bras A, Havet C, Villain G, Dernayka R, Duez C, Mattot V, Soncin F. Endothelial Cell Activation Is Regulated by Epidermal Growth Factor-like Domain 7 (Egfl7) during Inflammation. J. Biol. Chem. (2016) 291(46):24017-24028.
- Pannier D, Philippin-Lauridant G, Baranzelli MC, Bertin D, Bogart E, Delprat V, Villain G, Mattot V, Bonneterre J, Soncin F. High expression levels of egfl7 correlate with low endothelial cell activation in peritumoral vessels of human breast cancer. Oncol. Lett. (2016) 12(2):1422-1428