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Yoann Rombouts

Summary

Cellular and Molecular Glycobiologist with an emphasis in host-pathogen interactions

 

Contribution to science and scientific interests

I have been working for many years in the field of structural glycobiology in the context of mycobacterial infection and (auto)immunity (rheumatoid arthritis, RA). I received my PhD in biochemistry and glycobiology from the University of Lille in December 2010. My PhD work in the Unit of Structural and Functional Glycobiology (Supervisors: Dr. Yann Guérardel and Prof. Elisabeth Elass-Rochard) dealt with the structural characterization of mycobacterial cell envelop glycoconjugates by nuclear magnetic resonance, gas chromatography and mass spectometry and the analysis of their immunomodulatory properties on macrophages. After spending a year as a postdoctoral fellow in the same laboratory, my keen interest in translational research led me to join the Department of Rheumatology and the Center for Proteomics and Metabolomics at the Leiden University Medical Center (LUMC, The Netherlands) to work on the structure-function relationship of (auto)antibody glycosylation in RA (Supervisors: Prof René Toes & Prof. Manfred Wuhrer). During this postdoctoral period (2011-2014), I gained further knowledge in immunology, acquired experience in the high throughput analysis of glycans using mass spectrometry, and supervised the work of several Master and PhD students. My research and mentoring efforts contributed to obtaining 4 international research grants, the most recent being the “GlyCoCan” Marie Skłodowska-Curie Innovative European Training Networks project, started in September 2015, in which I am one of the principal investigators. In 2015, I was recruited as a permanent researcher by the French National Center for Scientific Research (CNRS) to work on the glycobiology of immune cell during infection

 

Current Position

CNRS associate researcher, Institute of Pharmacology and Structural biology, UMR 5089 CNRS- University of Toulouse, France (Laboratory of Dr. Olivier Neyrolles)

 

Projects

Role of macrophage glycosylation in regulating anti-microbial defense against Mycobacterium tuberculosis

Macrophages (MFs) and their precursors, monocytes, play a central role in host protecting immunity and contribute to the pathogenesis of inflammatory and degenerative diseases. Accumulating scientific evidences have emphasized the crucial roles of glycosylation in the modulation of both innate and adaptive immune responses. This project aims at exploiting transcriptomics and mass spectrometry-based glycomic and glycoproteomic approaches to characterize the changes in glycosylation accompanying the differentiation of monocytes into macrophages and the subsequent activation and polarization of macrophages during pathological processes. The causal and consequential implications accompanying pathophysiological changes will be addressed and validated in the context of infection by Mycobacterium tuberculosis (Mtb), the ethiological agent of tuberculosis in human, whereby the translational values of identified glyco-signatures will be evaluated.

 

Staff: Aurélien Boyancé, Karine Pingris & Y. Rombouts

Funding: Young Investigator Grant from the French National Research Agency (2017-2019; Coordinator: Y. Rombouts)

 

Deciphering the ligands and signaling pathways of the Dendritic cell immunoreceptor

The dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor mainly expressed by dendritic cells (DCs), macrophages and neutrophils. DCIR contains an immunoreceptor tyrosine-based inhibition motif (ITIM) which is essential for inducing immunological tolerance, through the recruitment of phosphatases including SHP-1 and SHP-2. Accordingly, mice deficient in Dcir1 (the closest murine homolog human DCIR) generally develop a stronger immune response to pathogen and are also more susceptible to aging-associated or experimentally induced antibody- and T cell-mediated autoimmune disorders than wild-type (WT) animals. We recently discovered that Dcir1 impairs anti-mycobacterial Th1 immune response through sustaining type I interferon (IFN)-mediated down-modulation of interleukin (IL)-12 in a SHP-2-dependent manner. Increased IL-12 production and Th1 activation in Mtb-infected Dcir1-KO animals translated into reduced bacterial burden in the lungs but also into increased immunopathology. Surprisingly, we found that Dcir1 does not recognize Mtb ligands, strongly suggesting that this receptor binds yet uncharacterized endogenous « danger » ligand(s), produced during inflammation. The central tenet of this project is to characterize both the endogenous ligand(s) and signaling pathway of DCIR to understand how DCIR sustain the type-I IFN axis in DCs.   

 

Staff: Tamara Sneperger, Giulia Trimaglio & Y. Rombouts

Funding: Fondation pour la Recherche Médicale (Coordinator: Olivier Neyrolles)

 

Role of the dendritic cell immunoreceptor (DCIR) in the regulation of anti-tumor immunity

As mentioned above, DCIR has been shown to regulate the immune responses in various pathological contexts including infection and auto-immunity. In contrast and despite the fact that DCIR is highly expressed by tumor-associated macrophages (TAMs) and dendritic cells, nothing is known about the role played by this C-type lectin in regulating tumor development and anti-tumor immunity. This project aims at exploring this avenue within the specific context of colorectal cancer which remains a major health burden being the third most common cancer in men and the second in women.

 

Staff: Giulia Trimaglio, André Colom & Y. Rombouts

Funding: H2020-MSCA-ITN GlycoCan (2015-2019: Coordinator: Manfred Wuhrer)

 

Short CV

 

EDUCATION

 

INSTITUTION AND LOCATION

DEGREE

 

Completion Date

 

FIELD OF STUDY

 

University of Lille, France

 

Bachelor

06/2005

Biochemistry

University of Lille, France

 

MSc

 

06/2007

 

Biology and Health, biochemistry

University of Lille, France

PhD

12/2010

Analytical Biochemistry and  Glycobiology

 

 

POSITIONS AND HONORS

 

Positions and employment

  • 2007-2010:  PhD Fellow, Unit for Structural and functional Glycobiology, UMR 8576 CNRS-University of Lille, France (Supervisors: Yann Guérardel; Co-director: Elisabeth Elass-Rochard)
  • 2010-2011:  Temporary teacher and postdoctoral researcher, Unit for Structural and functional Glycobiology, UMR 8576 CNRS-University of Lille, France.
  • 2011-2014:  Postdoctoral Researcher, Department of Rheumatology & Center for Proteomics and metabolomics, Leiden University Medical Center, The Netherlands (Supervisors: Prof. René Toes & Prof. Manfred Wuhrer)
  • Since 2015:  CNRS researcher, Institute of Pharmacology and Structural biology, UMR 5089 CNRS- University of Toulouse, France (Laboratory of Dr. Olivier Neyrolles)

 

Other experience and professional memberships

 

  • Currently Ph.D director of Giulia Trimaglio and Aurélien Boyancé
  • Member of the “Groupe Français des Glycosciences” (2008-2013), “Société Française de Biochimie et Biologie Moléculaire” (2011-2012) and Dutch Society for Immunology (2012-2015)
  • Expert referee for scientific journals, including Cell Reports, Journal of Proteomics, Frontiers in Immunology, Frontiers in microbiology, Glycoconjugates Journal, Plos one.
  • Currently guest editor for Frontiers in Immunology/microbiology on the research topics “The Mononuclear Phagocyte System in Infectious Disease”
  • Director of the local scientific animation committee in charge of organizing meetings and other scientific actions.

 

Honors

 

2007-2010 National Science doctoral fellowship at University of Lille

2008 Best Poster Award at the “22èmes Journées du Groupe Français des Glucides”

2012 Best Oral Presentation Award at the “24èmes  Journées du Groupe Français des Glucides”

2015 Best Poster Award at the 11th jenner glycobiology and medicine symposium

2017 International Glycoconjugate Organization (IGO) Young Glycoscientist Award

 

SCIENTIFIC ACHIEVEMENTS

My scientific achievements consist of 37 research articles, accumulating a citation index of 632 with an h-index of 16, according to Scopus (https://www.scopus.com/authid/detail.uri?authorId=34979269700).

 

5 SELECTED PUBLICATIONS

 

  • Hafkenscheid L, Bondt A, Scherer HU, Huizinga TW, Wuhrer M, Toes RE, Rombouts Y. Structural Analysis of Variable Domain Glycosylation of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Reveals the Presence of Highly Sialylated Glycans. Mol Cell Proteomics. 2017 Feb;16(2):278-287.
  • Rombouts Y, Willemze A, van Beers JJ, Shi J, Kerkman PF, van Toorn L, Janssen GM, Zaldumbide A, Hoeben RC, Pruijn GJ, Deelder AM, Wolbink G, Rispens T, van Veelen PA, Huizinga TW, Wuhrer M, Trouw LA, Scherer HU, Toes RE. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Ann Rheum Dis. 2016 Mar;75(3):578-85.
  • Rombouts Y, Ewing E, van de Stadt LA, Selman MH, Trouw LA, Deelder AM, Huizinga TW, Wuhrer M, van Schaardenburg D, Toes RE, Scherer HU. Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis. Ann Rheum Dis. 2015 Jan;74(1):234-41.
  • Rombouts Y, Brust B, Ojha AK, Maes E, Coddeville B, Elass-Rochard E, Kremer L, Guerardel Y. Exposure of mycobacteria to cell wall-inhibitory drugs decreases  production of arabinoglycerolipid related to Mycolyl-arabinogalactan-peptidoglycan metabolism. J Biol Chem. 2012 Mar 30;287(14):11060-9.
  • Rombouts Y, Elass E, Biot C, Maes E, Coddeville B, Burguière A, Tokarski C, Buisine E, Trivelli X, Kremer L, Guérardel Y. Structural analysis of an unusual bioactive N-acylated lipo-oligosaccharide LOS-IV in Mycobacterium marinum. J Am Chem Soc. 2010 Nov 17;132(45):16073-84.