Vivès Team

Scientific activity of the SAGAG-Vivès team

Heparan sulfate (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

The team
Scientific networks
Publications of the team

The team

Equipe SAGAG-Vivès

 Yara AWAD, PhD student
 Rebecca-Joe Boustany, PhD student
 Evelyne Gout, IE CNRS
 Catarina Marques, PhD student (co-supervision with Porto university)
 Gabriela Rosca, Master 1
 Romain Vivès (team leader), DR CNRS



A new inhibitor targeting the Sulfs !
(Collaboration with the University of Oxford)

More news (Archives)


ANR, UGA, Glyco@Alps...

Scientific networks

National scientific collaborations

Dr. D. Bonnaffé/C. le Narvor, ICMMO, Orsay
Dr. R. Daniel, LAMBE, Evry
Dr. O. Filhol-Cochet, CEA/Biosanté, Grenoble
Dr. F. Lecaille, CEPR, Tours
Dr. B. Marteyn IBMC, Strasbourg

Interational scientific collaborations

Dr. S. Grazioli/ N. Veraldi, HUG, Genève, Suisse
Dr. C. Reis/ A. Magalhaes, I3S, Porto, Portugal
Dr. A. Russel, Oxford univ., Oxford, UK
Dr. J. van den Born, Groningen univ., Groningen, The Netherlands
Dr. E. Schmidt, Colorado univ., Denver, USA
Dr. X. Yue, Louisiana univ., New Orleans, USA

The GDR « Gagosciences »

Romain Vivès was the coordinator of GDR CNRS3739 "Gagosciences" (2016-2020). This GDR was created to bring together French research teams studying GAGs within a structured network, built around diversified skills and complementary approaches, and promoting a multidisciplinary approach to advancing knowledge in glycosciences. The research carried out by the member teams was organized around 3 main areas of expertise (Biology, Chemistry and Methodological developments), and the GDR’s ambition was to encourage exchanges between these different disciplines.



Romain Vivès is coordinator of the IDEX-UGA Glyco@Alps program. The Glyco@Alps network explores the fascinating complexity and structural diversity of sugars, including those from Alpine biodiversity, and focuses on their exploitation in biopharmaceuticals, medical diagnostics, personalized medicine, materials, environmental sustainability and innovative bio-industries. It brings together some 100 researchers from the Grenoble region, from 21 different laboratories.


Publications of the team


A biological guide to glycosaminoglycans : current perspectives and pending questions.
Ricard-Blum S, Vivès RR, Schaefer L, Götte M, Merline R, Passi A, Heldin P, Magalhães A, Reis CA, Skandalis SS, Karamanos NK, Perez S, Nikitovic D.
FEBS J. 2024 Mar 18. ⟨10.1111/febs.17107⟩

BMP2 binds non-specifically to PEG-passivated biomaterials and induces substantial signaling
Jean Le Pennec , Amaury Guibert , Romain R. Vivès, Elisa Migliorini
BioRXiV ⟨10.1101/2024.03.14.585026⟩


Functional and structural insights into human N‐deacetylase/N‐sulfotransferase activities
Sylvain D Vallet, Thibault Annaval, Romain R Vives, Emeline Richard, Jerome Hénault, Christine Le Narvor, David Bonnaffé, Bernard Priem, Rebekka Wild, Hugues Lortat‐jacob
Proteoglycan Research, 2023, 1 (3), pp.e8. ⟨10.1002/pgr2.8⟩

Glycosaminoglycans : what remains to be deciphered ?
Serge Perez, Olga Makshakova, Jesus Angulo, Emiliano Bedini, Antonella Bisio, Jose Luis de Paz, Elisa Fadda, Marco Guerrini, Michal Hricovini, Milos Hricovini, Frederique Lisacek, Pedro M. Nieto, Kevin Pagel, Giulia Pairardi, Ralf Richter, Sergey A. Samsonov, Romain A. Vivès, Dragana Nikitovic, Sylvie Ricard Blum
JACS Au, 2023, ⟨10.1021/jacsau.2c00569⟩

Low-molecular weight sulfated marine polysaccharides : Promising molecules to prevent neurodegeneration in mucopolysaccharidosis IIIA ?
Noemi Veraldi, Isabelle Dentand Quadri, Yohan van de Looij, Laura Malaguti Modernell, Corinne Sinquin, Agata Zykwinska, Benjamin B. Tournier, Fabien Dalonneau, Honglian Li, Jin-Ping Li, Philippe Millet, Romain Vives, Sylvia Colliec Jouault, Ariane de Agostini, Eduardo Farias Sanches, Stéphane V. Sizonenko
Carbohydrate Polymers, 2023, 320, pp.121214. ⟨10.1016/j.carbpol.2023.121214⟩

Modified minimal-size fragments of Heparan Sulfate as inhibitors of endosulfatase-2 (Sulf-2)
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain Vives, Angela Russell
Chemical Communications, In press, ⟨10.1039/D3CC02565A⟩

Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry
Ilham Seffouh, Mélanie Bilong, Cédric Przybylski, Nesrine El Omrani, Salomé Poyer, Guillaume Lamour, Marie-Jeanne Clément, Rebecca-Joe Boustany, Evelyne Gout, Florence Gonnet, Romain R Vivès, Régis Daniel
Scientific Reports, 2023, 13 (1), ⟨10.1038/s41598-023-49147-5⟩

Sweet but Challenging : Tackling the Complexity of GAGs with Engineered Tailor‐Made Biomaterials
Jean Le Pennec, Catherine Picart, Romain R Vivès, Elisa Migliorini
Advanced Materials, 2023, ⟨10.1002/adma.202312154⟩


Binding of heparan sulfate to human cystatin C modulates inhibition of cathepsin L : Putative consequences in mucopolysaccharidosis
Sophie Denamur, Thibault Chazeirat, Martyna Maszota-Zieleniak, Romain Vivès, Ahlame Saidi, Fuming Zhang, Robert J. Linhardt, François Labarthe, Sergey A. Samsonov, Gilles Lalmanach, Fabien Lecaille
Carbohydrate Polymers, 2022, 293, pp.119734. ⟨10.1016/j.carbpol.2022.119734⟩

Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19
Noemi Veraldi, Romain Vivès, Géraldine Blanchard-Rohner, Arna L’Huillier, Noemie Wagner, Marie Rohr, Maurice Beghetti, Ariane de Agostini, Serge Grazioli, Arnaud L’huillier
Journal of Molecular Medicine, In press, ⟨10.1007/s00109-022-02190-7⟩

Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity
Rana El Masri, Amal Seffouh, Caroline Roelants, Ilham Seffouh, Evelyne Gout, Julien Pérard, Fabien Dalonneau, Kazuchika Nishitsuji, Fredrik Noborn, Mahnaz Nikpour, Göran Larson, Yoann Crétinon, Mélanie Friedel-Arboleas, Kenji Uchimura, Régis Daniel, Hugues Lortat-Jacob, Odile Filhol, Romain R. Vivès
Cell Reports, 2022, 38 (11), pp.110516. ⟨10.1016/j.celrep.2022.110516⟩

Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates Heparan Sulfate biosynthesis and shapes gastric cancer cell motility and invasion
Catarina Marques, Juliana Poças, Catarina Gomes, Isabel Faria-Ramos, Celso Reis, Romain Vivès, Ana Magalhães
Journal of Biological Chemistry, 2022, pp.102546. ⟨10.1016/j.jbc.2022.102546⟩

Preparation and Characterization of Heparan Sulfate-Derived Oligosaccharides to Investigate Protein–GAG Interaction and HS Biosynthesis Enzyme Activity
Cédric Laguri, Rabia Sadir, Evelyne Gout, Romain Vivès, Hugues Lortat-Jacob
Glycosaminoglycans, 2303, Springer US, pp.121-137, 2022, Methods in Molecular Biology, ⟨10.1007/978-1-0716-1398-6_11⟩

Neutrophils degranulate GAG-containing proteoglycofili, which block Shigella growth and degrade virulence factors
A.C. André, M. Valente Barroso, J. Skerniskyte, M. Siegwald, V. Paul, L. Debande, C. Ridley, I. Svahn, S. Rigaud, J.Y. Tinevez, R.R. Vivès, P.J. Sansonetti, D.J. Thornton and B.S. Marteyn.
BioRxiv 2022 ⟨10.1101/2022.02.08.479570⟩


Heparan sulfate biosynthesis and sulfation profiles as modulators of cancer signalling and progression
Catarina Marques, Celso Reis, Romain Vivès, Ana Magalhães
Frontiers in Oncology, 2021, 11, pp.718752. ⟨10.3389/fonc.2021.778752⟩

Hypercholesterolemia in Progressive Renal Failure Is Associated with Changes in Hepatic Heparan Sulfate - PCSK9 Interaction
Pragyi Shrestha, Saritha Adepu, Romain R. Vivès, Rana El Masri, Astrid Klooster, Fleur Kaptein, Wendy Dam, Stephan J L Bakker, Harry Van Goor, Bart van de Sluis ; Jacob van Den Born
Journal of the American Society of Nephrology, 2021, 32 (6), pp.1371-1388. ⟨10.1681/ASN.2020091376⟩

Proteinuria converts hepatic heparan sulfate to an effective proprotein convertase subtilisin kexin type 9 enzyme binding partner
Pragyi Shrestha, Saleh Yazdani, Romain Vivès, Rana El Masri, Wendy Dam, Bart van de Sluis, Jacob van den Born
Kidney International, 2021, ⟨10.1016/j.kint.2021.01.023⟩

Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches
Aurelien Kerever, Fumina Nagahara, Kazuko Keino-Masu, Masayuki Masu, Toin van Kuppevelt, Romain Vivès, Eri Arikawa-Hirasawa
Glycobiology, 2021, ⟨10.1093/glycob/cwab081⟩

Role of the interactions of soft hyaluronan nanomaterials with CD44 and supported bilayer membranes in the cellular uptake
Raul Diaz-Salmeron, Jean-Philippe Michel, Hicheme Hadji, Evelyne Gout, Romain. Vivès, Gilles Ponchel, Kawthar Bouchemal
Colloids and Surfaces B : Biointerfaces, 2021, 205, pp.111916. ⟨10.1016/j.colsurfb.2021.111916⟩


Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity
Thibault Annaval, Rebekka Wild, Yoann Crétinon, Rabia Sadir, Romain Vivès, Hugues Lortat-Jacob
Molecules, 2020, 25 (18), pp.4215. ⟨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, 11, ⟨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, 11, ⟨10.3389/fimmu.2020.00732⟩


A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry
Cédric Przybylski, Véronique Bonnet, Romain R Vivès
Chemical Communications, 2019, 55, pp.4182-4185. ⟨10.1039/C9CC00254E⟩

A proliferation‐inducing ligand–mediated anti‐inflammatory response of astrocytes in multiple sclerosis
Laurie Baert, Mahdia Benkhoucha, Natalia Popa, Mashal C Ahmed, Benoit Manfroi, Jean Boutonnat, Nathalie Sturm, Gilda Raguenez, Marine Tessier, Olivier Casez, Romain Marignier, Mitra Ahmadi, Alexis Broisat, Catherine Ghezzi, Cyril Rivat, Corinne Sonrier, Michael Hahne, Dominique L. Baeten, Romain R Vivès, Hugues Lortat-Jacob, Patrice N. Marche, Pascal Schneider, Hans P Lassmann, José Boucraut, Patrice H Lalive, Bertrand Huard
Annals of Neurology, 2019, 85 (3), pp.406-420. ⟨10.1002/ana.25415⟩

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
Amal Seffouh, Rana El Masri, Olga N Makshakova, Evelyne Gout, Zahra El Oula Hassoun, Jean-Pierre Andrieu, Hugues Lortat-Jacob, Romain R Vivès
Cellular and Molecular Life Sciences, 2019, 76 (9), pp.1807-1819. ⟨10.1007/s00018-019-03027-2⟩

Heparan sulfate in chronic kidney diseases : Exploring the role of 3-O-sulfation
Laura E Ferreras, Anna Moles, Gerhard Situmorang, Rana El Masri, Imogen Wilson, Katie Cooke, Emily Thompson, Marion Kusche-Gullberg, Romain R Vivès, Neil Sheerin, Simi Ali
Biochimica et Biophysica Acta (BBA) - General Subjects, 2019, 1863 (5), pp.839-848

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⟩

Mass spectrometry analysis of the human endosulfatase Hsulf-2
Ilham Seffouh, Cédric Przybylski, Amal Seffouh, Rana El Masri, Romain R Vivès, Florence Gonnet, Régis Daniel
Biochemistry and Biophysics Reports, 2019, 18, pp.100617. ⟨10.1016/j.bbrep.2019.01.010⟩

Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase
Claire Debarnot, Yoan Monneau, Veronique Roig-Zamboni, Vincent Delauzun, Christine Le Narvor, Emeline Richard, Jérôme Hénault, Adeline Goulet, Firas Fadel, Romain R Vivès, Bernard Priem, David Bonnaffé, Hugues Lortat-Jacob, Yves Bourne
Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (14), pp.6760-6765. ⟨10.1073/pnas.1818333116⟩


Genetic and enzymatic characterization of 3-O-sulfotransferase SNPs associated with Plasmodium falciparum parasitaemia
Ngoc Thy Nguyen, Romain R Vivès, Magali Iché-Torres, Vincent Delauzun, Els Saesen, Veronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
Glycobiology, 2018, 28 (7), pp.534-541. ⟨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
Biochimica et Biophysica Acta (BBA) - General Subjects, 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, 2017, 12 (6), pp.e0178940. ⟨10.1371/journal.pone.0178940.eCollection2017⟩

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, 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, 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, Cosset François-Loïc, Denis Gerlier, Romain R Vivès, Branka Horvat
mBio, 2015, 6 (2), pp.e02427. ⟨10.1128/mBio.02427-14⟩

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 Muñoz-García, Eric Chabrol, Romain Vivès, Aline Thomas, José de Paz, Javier Rojo, Anne Imberty, Franck Fieschi, Pedro Nieto, Jesus Angulo
Journal of the American Chemical Society, 2015, 137 (12), pp.4100-4110. ⟨10.1021/ja511529x⟩

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, 2015, 27 (10), pp.2054-67. ⟨10.1016/j.cellsig.2015.07.017⟩


Post-Synthetic Regulation of HS Structure : The Yin and Yang of the Sulfs in Cancer.
Romain R Vivès, Amal Seffouh, Hugues Lortat-Jacob
Frontiers in Oncology, 2014, 3, pp.331. ⟨10.3389/fonc.2013.00331⟩

News (archives)

15 scientists give their views on GAG research and future prospects


Higlights on our latest work on the Sulfs !





PhD students :
Jean Le pennec (co-direction IRIG/Biosanté), 2020-2023
Yoann Crétinon, 2018-2022
Rubal Ravinder (co-direction CERMAV), 2017-2021
Rana El Masri, 2016-2019
Amal Seffouh, 2013-2016

Post-docs, Engineers, technicians :

Mélanie Friedel (CDD AI), 2021-2023
Fabien Dalonneau (CDD AI), 2019-2020
Elodie Henriet (CDD engineer), 2013-2014

Internships :
Palig Karaminassian (Master 2), 2023
Marina Callandret (Master 2), 2021
Gaël Méli-Duthoit (BTS), 2018-2020
Mayssa Ghaddar (Master 2), 2018
Zahra al Oula Hassoun (Master 2), 2017
Elisa Tournebize (Master 1), 2016
Hugo Fumat (Licence 3), 2015
Adrien Laroche (Licence 3), 2014

Equipe SAGAG-Vivès, 2018