Director of Research at INSERM


LIMMS/CNRS-IIS, The University of Tokyo, Lille, France


fabrice.soncin(a)inserm.fr

EDUCATION

  • 1998    Habilitation à Diriger des Recherches, Doctoral School of Life & Health, University of Lille, Lille
  • 1990    PhD in Cell & Molecular Development Biology, University of Paris VI, Paris

PROFESSIONAL ACTIVITIES

  • 2024-… Deputy director of SMMiL-E
  • 2005-… Directeur de Recherche INSERM – Tenure position
  • 1994-2005   Chargé de Recherche INSERM – Tenure position
  • 1994-1995   Instructor, Dana Farber Cancer Institute – Harvard Medical School, Boston, MA, USA
  • 1992-1993   Instructor, Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA, USA
  • 1991     Post-doctoral research fellow, Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, USA

MISCELLANEOUS (current)

  • Member of the Administration Board of the French Angiogenesis Society
    2007-2011: 1st President 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.

            We 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 (2018-24)

  • Garnier N, Sane F, Massara L, Soncin F, Gosset P, Hober D, Szunerits S, Engelmann I
    Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection.
    Viruses 2023, 15(5), 1177.
  • Messelmani T, Le Goff A, Soncin F, Gilard F, Souguir Z, Maubon N, Gakière B, Legallais C, Leclerc E, Jellali R
    Investigation of the metabolomic crosstalk between liver sinusoidal endothelial cells and hepatocytes exposed to paracetamol using organ-on-chip technology.
    Toxicology 2023 Jun 15;492:153550
  • Gaggero S, Martinez-Fabregas J, Cozzani A, Fyfe P, Leprohon M, Yang J, Thomasen FE, Winkelmann H, Magnez R, Conti AG, Wilmes S, Pohler E, van Gijsel Bonnello M, Thuru X, Quesnel B, Soncin F, Piehler J, Lindorff-Larsen K, Roychoudhuri R, Moraga I, Mitra S
    IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein.
    Science Immunology 2022 Dec 9;7(78):eade5686.
  • Delprat V, Huart C, Feron O, Soncin F, Michiels C.
    The impact of macrophages on endothelial cells is potentiated by cycling hypoxia: enhanced tumor inflammation and metastasis.
    Front. Oncol. 2022 12:961753.
  • Garnier N, Pollet K, Fourcot M, Caplan M, Marot G, Goutay J, Labreuche J, Soncin F, Boukherroub R, Hober D, Szunerits S, Poissy J, Engelmann I
    Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role
    Clin. Transl. Med. 2022;12:e899
  • Delannoy E, Tellier G, Cholet J, Leroy AM, Treizebre A, Soncin F
    Multi-layered human blood vessels-on-chip via double viscous finger patterning
    Biomedicines 2022, 10(4), 797
  • Pinte S, Delfortrie S, Havet C, Villain G, Mattot V, Soncin F
    EGF repeats of epidermal growth factor-like domain 7 promote endothelial cell activation and tumor escape from the immune system
    Oncology Reports, 2022 Jan;47(1):8
  • Silvent J, Robin M, Bussola Tovani C, Wang Y, Soncin F, Delgado S, Azaïs T, Sassoye C, Giraud-Guille MM, Sire JY, Nassif N
    Collagen Suprafibrillar Confinement Drives the Activity of Acidic Calcium-Binding Polymers on Apatite Mineralization.
    Biomacromolecules 2021 Jul 12;22(7):2802-2814.
  • Danoy M, Jellali R, Tauran Y, Bruce J, Leduc M, Gilard F, Gakière B, Scheidecker B, Kido T, Miyajima A, Soncin F, Sakai Y, Leclerc E
    Characterization of the proteome and metabolome of human liver sinusoidal endothelial-like cells derived from induced pluripotent stem cells.
    Differentiation 2021 Jun 30;120:28-35.
  • Usuba R, Pauty J, Soncin F*, Matsunaga YT*
    EGFL7 regulates sprouting angiogenesis and endothelial integrity in a human blood vessel model.
    Biomaterials 2019 Mar;197:305-316
    *co-last authors
  • Villain G, Lelievre E, Broekelmann T, Gayet O, Havet C, Werkmeister E, Mecham R, Dusetti N, Soncin F, Mattot V.
    MAGP-1 and fibronectin control EGFL7 functions by driving its deposition into distinct endothelial extracellular matrix locations.
    FEBS J. 2018 Dec;285(23):4394-4412
  • 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 Dec 20. pii: S2352-3964 (17) 30497-8
    *co-last authors
  • Villain G, Poissonnier L, Noueihed B, Bonfils G, Rivera JC, Chemtob S, Soncin F, Mattot V.
    miR-126-5p promotes retinal endothelial cell survival through SetD5 regulation in neurons.
    Development 2018 Jan 8;145(1)
  • d’Audigier C, Susen S, Blandinieres A, Mattot V, Saubamea B, Rossi E, Nevo N, Lecourt S, Guerin CL, Dizier B, Gendron N, Caetano B, Gaussem P, Soncin F, Smadja DM
    Egfl7 represses the vasculogenic potential of human endothelial progenitor cells
    Stem Cell Reviews and Reports, 2018 14(1):82-91.