Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / Vivès Romain

the SAGAG-Vivès team

Head of team: Romain Vivès


Scientific activity of the SAGAG-Vivès team

Heparan sulfates (HS) is a sulfated polysaccharide that is a major component of the glycocalyx, the thick layer of glycoconjugates found on the surface of most animal cells (1). Thanks to this strategic positioning at the interface between the cell and its external environment, HS encounters, binds and modulates the activity of a multitude of protein ligands, and thus participates in most major cellular processes (2). These extensive biological properties arise from the presence of specific saccharide units within the polysaccharide (3), which structure and sulfation define a "glycocode" gathering recognition and interaction information for the different protein partners. The structure of HS must therefore be finely regulated, to allow the cell to adapt its response to any external stimuli. Recently, it has been shown that a family of sulfatases, the Sulfs, play a major role of glycobiological regulators, by modifying the sulfation of HS and their interaction properties (4).

SAGAG Vivès : HS

Our team is particularly interested in this enzymatic mechanism, which represents the only post-synthetic molecular machine able to regulate and modify the glycocode of HS. In this context, our work focuses on studying the structural features of the enzyme (5), its molecular organization, substrate specificities, and the post-translational modifications essential for its activity. We also investigate its enzyme activity and function (6), using in vitro, cell-based and in vivo bioassays available in the laboratory or through the numerous national and international collaborations established on the subject. Finally, we aim to develop inhibitors based on HS mimetics for the development of new anti-cancer therapeutic approaches targeting the Sulfs (7).

SAGAG Vivès : Study of the Sulfs

News

The SAGAG-Vivès team is recruiting!

We are opening a 18-24 month position for an engineer. He/She will be in charge of this multidisciplinary project, which involves the production of recombinant proteins (in eukaryotic and prokaryotic expression systems), the preparation and screening of oligosaccharide substrate libraries using functional assay (SPR, enzyme assays…) and the functional analysis of Sulf activity using cellular assays (proliferation, migration…).

More information....

News (archives)

More news....

Team members

Members

  • Evelyne Gout (IE CNRS)
  • Yoann Crétinon (PhD student)
  • Rubal Ravinder (collab. CERMAV, PhD student)
  • Romain Vivès (DR CNRS)

Alumni (since 2014)

  • Rana El Masri (PhD student)
  • Gaël Méli-Duthoit (BTS student)
  • Mayssa Ghaddar (Master 2)
  • Zahra al Oula Hassoun (Master 2), currently PhD student (Liège, Belgium).
  • Elisa Tournebize (Master 1), currently working (SANOFI-Pasteur, Lyon).
  • Hugo Fumat (Licence 3)
  • Elodie Henriet (CDD ingénieur), currently PhD student (Orleans, France).
  • Adrien Laroche (Licence 3)
  • Amal Seffouh (thèse), currently post-doc (Montreal, Canada).

Fundings

ANR, UGA, Glyco@Alps...

Scientific networks

National scientific collaborations

  • Dr. D. Bonnaffé, ICMMO, Orsay
  • Dr. Y. Bourne, AFMB, Marseille
  • Dr. R. Daniel, LAMBE, Université d’Evry-Val d’Essonne
  • Dr. O. Filhol-Cochet, CEA-BIG, Grenoble
  • Dr. S. Halila, CERMAV, Grenoble
  • Dr. B. Horvat, ENS, Lyon
  • Dr. B. Huard, IAB, Grenoble
  • Dr. C. le Narvor, ICMMO, Orsay

International scientific collaborations

  • Dr. S. Ali, Newcastle University, UK
  • Dr. K. Dobra , University of Stockholm, Sweden
  • Dr. E. Schmidt, University of Colorado, USA
  • Dr. J. Van den Born, University of Groningen, the Netherlands
  • Dr. X. Yue, Louisiana State University, USA

The GDR « Gagosciences »

Romain Vivès is coordinator of the GDR CNRS3739 « Gagosciences ». This GDR has been created to federate French research teams working on GAGs within a structured network gathering complementary expertise. The aim of the GDR GAG is to promote multidisciplinary research in glycoscience within 3 major disciplinary fields: biology, chemistry and methodological developments.

More information...

GDR GAG

Glyco@Alps

Romain Vivès is member of the executive committee of the Glyco@Alps IDEX-UGA program (coordinator of WP2). Glyco@Alps explores the fascinating structural diversity and complexity of sugars, including those found in the Alpine biodiversity, and focuses on their exploitation for biopharmaceuticals, medical diagnostics, personalized medicine, materials, environmental sustainability and innovative bio-industries. With the involvement of around 100 scientists of different domains, Glyco@Alps will highlight the University Grenoble Alpes as the first glycoscience center in France.

En savoir plus....

Glyc@Alps


Recent publications

Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression
C. Marques, CA Reis, RR Vivès and A. Magalhães
Frontiers in Oncology, 2021, <10.3389/fonc.2021.778752.>

Preparation and characterization of Heparan sulfate derived oligosaccharides to investigate protein-GAG interaction and HS biosynthesis enzyme activity
C. Laguri, R. Sadir, E. Gout, R.R. Vivès and Hugues Lortat-Jacob
Methods in Molecular Biology , 2022, Vol. 2303, 121-137 <10.1007/978-1-0716-1398-6_11>

Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches
A. Kerever, F. Nagahara, K. Keino-Masu, M. Masu, T.H. van Kuppevelt, R.R. Vivès, and E. Arikawa-Hirasawa
Glycobiology , 2021, <10.1093/glycob/cwab081>

Interplay between CD44 receptor and passive membrane interactions of soft hyaluronan nano-platelets with cells
R. Diaz-Salmeron, J.P. Michel, R.R. Vivès, A. da Costa, S. Denis, H. Hadji, G. Ponchel and K. Bouchemal Colloids and Surfaces B: Biointerfaces , 2021, <10.1016/j.colsurfb.2021.111916>

Hypercholesterolemia in progressive renal failure associates with changes in hepatic heparan sulfate – PCSK9 interaction
. Shrestha, S. Adepu, R.R. Vivès, R. El Masri, A. Klooster, F. Kaptein, W. Dam, H.G.D Leuvenink, S. Bakker, H. van Goor, B. van de Sluis and J. van den Born
JASN , 2021, <10.1681/ASN.2020091376>

Proteinuria converts hepatic heparan sulfate to effective proprotein convertase subtilisin kexin type 9 enzyme binding partner
P. Shrestha, S. Yazdani, R.R. Vivès, R. EI Masri, W. Dam, B.van de Sluis and J.van den Born
Kidney Int. , 2021, <10.1016/j.kint.2021.01.023>

Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity
Annaval T, Wild R, Crétinon Y, Sadir R, Vivès RR, Lortat-Jacob H.
Molecules, 2020, <10.3390/molecules25184215>

HS and Inflammation: A Potential Playground for the Sulfs?
Rana El Masri, Yoann Crétinon, Evelyne Gout, Romain R Vivès
Frontiers in Immunology, 2020, <10.3389/fimmu.2020.00570>

MASP-2 Is a Heparin-Binding Protease; Identification of Blocking Oligosaccharides
Ditmer Talsma, Felix Poppelaars, Wendy Dam, Anita Meter-Arkema, Romain R Vivès, Peter Gál, Geert-Jan Boons, Pradeep Chopra, Annamaria Naggi, Marc Seelen, Stephan Berger, Mohamed Daha, Coen Stegeman, Jacob van den Born
Frontiers in Immunology, 2020, <10.3389/fimmu.2020.00732>

Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses
Kaori Oshima, Xiaorui Han, Yilan Ouyang, Rana El Masri, Yimu Yang, Sarah Haeger, Sarah Mcmurtry, Trevor Lane, Pavel Davizon-Castillo, Fuming Zhang, Xinping Yue, Romain R Vivès, Robert Linhardt, Eric Schmidt
American Journal of Physiology - Lung Cellular and Molecular Physiology, 2019, <10.1152/ajplung.00175.2019>

A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry
Przybylski C, Bonnet V, Vivès RR
Chem Commun (Camb), 2019, <10.1039/c9cc00254e>

Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase
Debarnot C, Monneau YR, Roig-Zamboni V, Delauzun V, Le Narvor C, Richard E, Hénault J, Goulet A, Fadel F, Vivès RR, Priem B, Bonnaffé D, Lortat-Jacob H, Bourne Y
Proc Natl Acad Sci U S A, 2019, <10.1073/pnas.1818333116>

Heparan sulfate in chronic kidney diseases: Exploring the role of 3-O-sulfation
Ferreras L, Moles A, Situmorang GR, El Masri R, Wilson IL, Cooke K, Thompson E, Kusche-Gullberg M, Vivès RR, Sheerin NS, Ali S.
Biochim Biophys Acta Gen Subj, 2019, 1863(5):839-848. <10.1016/j.bbagen.2019.02.009>

Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate
Seffouh A, El Masri R, Makshakova O, Gout E, Hassoun ZEO, Andrieu JP, Lortat-Jacob H, Vivès RR.
Cell Mol Life Sci. 2019 <10.1007/s00018-019-03027-2>

Mass spectrometry analysis of the human endosulfatase Hsulf-2
Seffouh I, Przybylski C, Seffouh A, El Masri R, Vivès RR, Gonnet F, Daniel R.
Biochem Biophys Rep, 2019, 18:100617.
<10.1016/j.bbrep.2019.01.010.>

A proliferation-inducing ligand-mediated anti-inflammatory response of astrocytes in multiple sclerosis
Baert L, Benkhoucha M, Popa N, Ahmed MC, Manfroi B, Boutonnat J, Sturm N, Raguenez G, Tessier M, Casez O, Marignier R, Ahmadi M, Broisat A, Ghezzi C, Rivat C, Sonrier C, Hahne M, Baeten D, Vives RR, Lortat-Jacob H, Marche PN, Schneider P, Lassmann HP, Boucraut J, Lalive PH, Huard B.
Ann Neurol., 2019, 85:406-420. <10.1002/ana.25415>

Genetic and enzymatic characterization of 3-O-sulfotransferase SNPs associated with Plasmodium falciparum parasitaemia
Ngoc Thy Nguyen, Romain R Vivès, Magali Torres, Vincent Delauzun, Els Saesen, Veronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
Glycobiology, Oxford University Press (OUP), 2018, 〈10.1093/glycob/cwy038〉

A jasmonic acid derivative improves skin healing and induces changes in proteoglycan expression and glycosaminoglycan structure
Elodie Henriet, Sibylle Jäger, Christian Tran, Philippe Bastien, Jean-François Michelet, Anne-Marie Minondo, Florian Formanek, Maria Dalko-Csiba, Hugues Lortat-Jacob, Lionel Breton, Romain R Vivès
BBA - General Subjects, Elsevier, 2017, 1861 (9), pp.2250-2260. 〈10.1016/j.bbagen.2017.06.006〉

High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats
Ryanne S. Hijmans, Pragyi Shrestha, Sarpong Ka, Saleh Yazdani, Rana El Masri, Wilhelmina H. A. De Jong, Gerjan Navis, Romain R Vivès, Jacob van Den Born
PLoS ONE, Public Library of Science, 2017, 12 (6), pp.e0178940. 〈10.1371/journal.pone.0178940. eCollection 2017〉

Solution structure of CXCL13 and heparan sulfate binding show that GAG binding site and cellular signalling rely on distinct domains
Yoan Monneau, Lingjie Luo, Nehru Viji Sankaranarayanan, Balaji Nagarajan, Romain R Vivès, Françoise Baleux, Umesh R. Desai, Fernando Arenzana-Seidedos, Hugues Lortat-Jacob
Open Biology, Royal Society, 2017, 7, pp.170133. 〈10.1098/rsob.170133〉

The "in and out" of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate.
Rana El Masri, Amal Seffouh, Hugues Lortat-Jacob, Romain R Vivès

Glycoconjugate Journal, Springer Verlag, 2017, 34 (3), pp.285-298. 〈10.1007/s10719-016-9736-5〉

Heparan sulfate-dependent enhancement of henipavirus infection.
Cyrille Mathieu, Kévin P Dhondt, Marie Châlons, Stéphane Mély, Hervé Raoul, Didier Negre, François-Loïc Cosset, Denis Gerlier, Romain R Vivès, Branka Horvat
mBio, American Society for Microbiology, 2015, 6 (2), pp.e02427

Langerin-heparin interaction: two binding sites for small and large ligands as revealed by a combination of NMR spectroscopy and cross-linking mapping experiments.
Juan C Muñoz-García, Eric Chabrol, Romain R Vivès, Aline Thomas, José L De Paz, Javier Rojo, Anne Imberty, Franck Fieschi, Pedro M Nieto, Jesus Angulo
Journal of the American Chemical Society, American Chemical Society, 2015, 137 (12), pp.4100-10

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma
Ghazal Heidari-Hamedani, Romain R Vivès, Amal Seffouh, Nikolaos A Afratis, Arie Oosterhof, Toin H Van Kuppevelt, Nikos K Karamanos, Muzaffer Metintas, Anders Hjerpe, Katalin Dobra, Tünde Szatmári
Cellular Signalling, Elsevier, 2015, 〈10.1016/j.cellsig.2015.07.017〉

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma .
Ghazal Heidari-Hamedani, Romain R Vivès, Amal Seffouh, Nikolaos A Afratis, Arie Oosterhof, Toin H Van Kuppevelt, Nikos K Karamanos, Muzaffer Metintas, Anders Hjerpe, Katalin Dobra, Tünde Szatmári
Cellular Signalling, Elsevier, 2015, 27 (10), pp.2054-67