Valérie Wittamer

https://www.wittamer-lab.org/

Our research aims at providing novel insights into the basic biology of microglia, the resident immune cells of the central nervous system. In particular, we are interested in how the microglial network is established during vertebrate development, and subsequently maintained throughout life. Understanding these key aspects of microglia biology are of major importance since microglia are implicated in the pathology of most, if not all neurological disorders, and are now considered as major putative targets for therapeutic intervention in the field of neuroinflammation.

Our laboratory takes advantage of the strenghts of the zebrafish model system to address microglia development in ways not possible in other vertebrates. Because the first steps of microglia ontogeny occur early during embryogenesis, transparent transgenic zebrafish embryos offer great opportunities to characterize these processes in a non invasive way.

 

Our program relies on targeted genome editing gene manipulation using the TALEN and CRISPR technologies to manipulate microglia gene functions in vivo and examine the subsequent effects on microglia biology. We also perform live imaging analyses on fluorescent transgenic embryos to directly observe the behavior of microglial cells in vivo, as they interact in their microenvironment. In the long run, we also plan to develop zebrafish models of neurodegeneration and cancer that should prove instrumental for the analysis of microglia contribution in pathology and disease.

Valerie Wittamer (PI– Research Associate F.N.R.S)

(vwittame@ulb.ac.be) phone # +32(0) 2 555 3052

Valerie performed her graduate work in the laboratory of Marc Parmentier at Université Libre de Bruxelles (ULB) where she identified chemerin as the endogenous ligand of the orphan G protein-coupled receptor ChemR23. For this work, she was awarded the Belgian Galien Prize of Pharmacology in 2006. She then joined the laboratory of David Traver at University of California at San Diego (UCSD) where she developed novel zebrafish transgenic lines that provided new insights into the cellular biology of the zebrafish hematopoietic system.
Since starting her own laboratory in 2014, Valerie has received a Brains Back to Brussels Award from Innoviris and the Brussels-Capital Region, a Welbio Starting Grant Award from the Walloon Region, and Scholar Awards from the Fonds National de la Recherche Scientifique and the Minerve Foundation.

 

Marianne Caron (Lab Manager)
Marianne obtained her bachelor degree in biotechnologie at “Haute Ecole Provinciale de Hainaut” (HEPH Condorcet, Ath) in june 2014.
She joined the laboratory in early 2015 as our Lab Manager.
 

Mireia Rovira i Berger

Mireia obtained her PhD in the laboratory of Dr. Josep Planas in Fish Molecular Physiology at the University of Barcelona (UB) in 2016. In 2017 she joined the Evolutive Immunology research group led by Dr. Nerea Roher at the Biotechnology and Biomedicine Institute (IBB) in a collaborative project with Dr. María Isabel Pividori’s laboratory at the Autonomous University of Barcelona (UAB), to develop fish biosensors. Since 2018, she joined our lab as a postdoctoral researcher to work on microglia development and neuroregeneration.

 

Elodie Di Ruggiero (Ph.D student)
Elodie Di Ruggiero received her Master degree in Biochemistry and molecular and cellular biology from the Université libre de Bruxelles (ULB) in 2013. Elodie joined our laboratory in October 2014 as a PhD research fellow of the FNRS/FRIA. She is studying the implication of chemerin, a chemoattractant agent, in cancer biology

 

 

Omid Ghandaharian (Ph.D student)
Omid obtained his bachelor degree in molecular biology from “Ferdowsi University of Mashhad” in Iran. He then moved to Belgium to obtain his master degree in the same field in V.U.B. Since October 2014 he joined our lab as a Ph.D. student.

 

Giuliano Ferrero (Ph.D student)
Giuliano earned his master’s degree in Medical Biotechnology from the University of Turin. Awarded a UNI (ULB Neuroscience Institute) PhD fellowship, he joined our lab in 2015. Funded by an Aspirant FNRS grant, he is currently working on microglia development.

 

Jennifer Pozo Gomez (Ph.D student)
Jennifer Pozo Gomez obtained her Master degree in Biological Medicine from the Université Libre de Bruxelles (ULB) in June 2017.She joined our laboratory in October 2017 as a PhD student.Jennifer is studying the role of chemerin in tumorigenesis.

 

 

Magali Miserocchi (Master Student)
Magali Miserocchi obtained her bachelor degree in biomedical sciences at Université Libre de Bruxelles in 2016. She is currently doing her Master thesis in our lab. 

 

 

 

Microglia states and nomenclature: A field at its crossroads. Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, Amit I, Audinat E, Bechmann I, Bennett M, Bennett F, Bessis A, Biber K, Bilbo S, Blurton-Jones M, Boddeke E, Brites D, Brône B, Brown GC, Butovsky O, Carson MJ, Castellano B, Colonna M, Cowley SA, Cunningham C, Davalos D, De Jager PL, de Strooper B, Denes A, Eggen BJL, Eyo U, Galea E, Garel S, Ginhoux F, Glass CK, Gokce O, Gomez-Nicola D, González B, Gordon S, Graeber MB, Greenhalgh AD, Gressens P, Greter M, Gutmann DH, Haass C, Heneka MT, Heppner FL, Hong S, Hume DA, Jung S, Kettenmann H, Kipnis J, Koyama R, Lemke G, Lynch M, Majewska A, Malcangio M, Malm T, Mancuso R, Masuda T, Matteoli M, McColl BW, Miron VE, Molofsky AV, Monje M, Mracsko E, Nadjar A, Neher JJ, Neniskyte U, Neumann H, Noda M, Peng B, Peri F, Perry VH, Popovich PG, Pridans C, Priller J, Prinz M, Ragozzino D, Ransohoff RM, Salter MW, Schaefer A, Schafer DP, Schwartz M, Simons M, Smith CJ, Streit WJ, Tay TL, Tsai LH, Verkhratsky A, von Bernhardi R, Wake H, Wittamer V, Wolf SA, Wu LJ, Wyss-Coray T. Neuron. 2022 Nov 2;110(21):3458-3483. https://doi.org/10.1016/j.neuron.2022.10.020

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Guilliams M, Bonnardel J, Haest B, Vanderborght B, Wagner C, Remmerie A, Bujko A, Martens L, Thoné T, Browaeys R, De Ponti FF, Vanneste B, Zwicker C, Svedberg FR, Vanhalewyn T, Gonçalves A, Lippens S, Devriendt B, Cox E, Ferrero G, Wittamer V, Willaert A, Kaptein SJF, Neyts J, Dallmeier K, Geldhof P, Casaert S, Deplancke B, Ten Dijke P, Hoorens A, Vanlander A, Berrevoet F, Van Nieuwenhove Y, Saeys Y, Saelens W, Van Vlierberghe H, Devisscher L, Scott CL.Cell. 2022 Jan 5:S0092-8674(21)01481-1. doi: 10.1016/j.cell.2021.12.018. Online ahead of print.

Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis.Al Delbany D, Robert V, Dubois-Vedrenne I, Del Prete A, Vernimmen M, Radi A, Lefort A, Libert F, Wittamer V, Sozzani S, Parmentier M. Cancers (Basel). 2021 Oct 5;13(19):5000. doi: 10.3390/cancers13195000.

The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis. Dubois-Vedrenne I, Al Delbany D, De Henau O, Robert V, Vernimmen M, Langa F, Lefort A, Libert F, Wittamer V, Parmentier M. Oncotarget. 2021 Sep 14;12(19):1903-1919. doi: 10.18632/oncotarget.28056. eCollection 2021 Sep 14.

Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization. Ben Dhaou C, Mandi K, Frye M, Acheampong A, Radi A, De Becker B, Antoine M, Baeyens N, Wittamer V, Parmentier M. Angiogenesis. 2021 Sep 15. doi: 10.1007/s10456-021-09818-1. Online ahead of print.

A csf1rb mutation uncouples two waves of microglia development in zebrafish. Ferrero G, Miserocchi M, Di Ruggiero E, Wittamer V. Development. 2021 Jan 11;148(1):dev194241. doi: 10.1242/dev.194241.

Corrigendum: Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis. Dubois-Vedrenne I, De Henau O, Robert V, Langa F, Javary J, Al Delbany D, Vosters O, Angelats-Canals E, Vernimmen M, Luangsay S, Wittamer V, Parmentier M. Front Oncol. 2020 Jun 23;10:977. doi: 10.3389/fonc.2020.00977. eCollection 2020.

Yolk sac hematopoiesis: does it contribute to the adult hematopoietic system? Wittamer V, Bertrand JY. Cell Mol Life Sci. 2020 Oct;77(20):4081-4091. doi: 10.1007/s00018-020-03527-6. Epub 2020 May 13.

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes. Kuil LE, Oosterhof N, Ferrero G, Mikulášová T, Hason M, Dekker J, Rovira M, van der Linde HC, van Strien PM, de Pater E, Schaaf G, Bindels EM, Wittamer V, van Ham TJ. Elife. 2020 May 5;9:e53403. doi: 10.7554/eLife.53403.

The macrophage-expressed gene (mpeg) 1 identifies a subpopulation of B cells in the adult zebrafish. Ferrero G, Gomez E, Lyer S, Rovira M, Miserocchi M, Langenau DM, Bertrand JY, Wittamer V. J Leukoc Biol. 2020 Mar;107(3):431-443. doi: 10.1002/JLB.1A1119-223R. Epub 2020 Jan 7.

Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis. Dubois-Vedrenne I, De Henau O, Robert V, Langa F, Javary J, Al Delbany D, Vosters O, Angelats-Canals E, Vernimmen M, Luangsay S, Wittamer V, Parmentier M. Front Oncol. 2019 Nov 15;9:1253. doi: 10.3389/fonc.2019.01253. eCollection 2019.

Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish. Ferrero G, Mahony CB, Dupuis E, Yvernogeau L, Di Ruggiero E, Miserocchi M, Caron M, Robin C, Traver D, Bertrand JY, Wittamer V. Cell Rep. 2018 Jul 3;24(1):130-141. doi: 10.1016/j.celrep.2018.05.066.

An evolutionarily conserved program of B-cell development and activation in zebrafish. Page DM, Wittamer V, Bertrand JY, Lewis KL, Pratt DN, Delgado N, Schale SE, McGue C, Jacobsen BH, Doty A, Pao Y, Yang H, Chi NC, Magor BG, Traver D. Blood. 2013 Aug 22;122(8):e1-11. doi: 10.1182/blood-2012-12-471029. Epub 2013 Jul 16.

Development and characterization of anti-nitr9 antibodies. Shah RN, Rodriguez-Nunez I, Eason DD, Haire RN, Bertrand JY, Wittamer V, Traver D, Nordone SK, Litman GW, Yoder JA. Adv Hematol. 2012;2012:596925. doi: 10.1155/2012/596925. Epub 2012 Sep 24.

Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Bondue B, Wittamer V, Parmentier M. Cytokine Growth Factor Rev. 2011 Oct-Dec;22(5-6):331-8. doi: 10.1016/j.cytogfr.2011.11.004. Epub 2011 Nov 25.

Characterization of the mononuclear phagocyte system in zebrafish. Wittamer V, Bertrand JY, Gutschow PW, Traver D. Blood. 2011 Jun 30;117(26):7126-35. doi: 10.1182/blood-2010-11-321448. Epub 2011 Mar 15.

Developmental and tissue-specific expression of NITRs. Yoder JA, Turner PM, Wright PD, Wittamer V, Bertrand JY, Traver D, Litman GW. Immunogenetics. 2010 Feb;62(2):117-22. doi: 10.1007/s00251-009-0416-5. Epub 2009 Dec 12.

Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. Luangsay S, Wittamer V, Bondue B, De Henau O, Rouger L, Brait M, Franssen JD, de Nadai P, Huaux F, Parmentier M. J Immunol. 2009 Nov 15;183(10):6489-99. doi: 10.4049/jimmunol.0901037. Epub 2009 Oct 19.

Role of neutrophil proteinase 3 and mast cell chymase in chemerin proteolytic regulation. Guillabert A, Wittamer V, Bondue B, Godot V, Imbault V, Parmentier M, Communi D. J Leukoc Biol. 2008 Dec;84(6):1530-8. doi: 10.1189/jlb.0508322. Epub 2008 Aug 27.

Chemerin–a new adipokine that modulates adipogenesis via its own receptor. Roh SG, Song SH, Choi KC, Katoh K, Wittamer V, Parmentier M, Sasaki S. Biochem Biophys Res Commun. 2007 Nov 3;362(4):1013-8. doi: 10.1016/j.bbrc.2007.08.104. Epub 2007 Aug 27.

Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. Wittamer V, Bondue B, Guillabert A, Vassart G, Parmentier M, Communi D. J Immunol. 2005 Jul 1;175(1):487-93. doi: 10.4049/jimmunol.175.1.487.

Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. Vermi W, Riboldi E, Wittamer V, Gentili F, Luini W, Marrelli S, Vecchi A, Franssen JD, Communi D, Massardi L, Sironi M, Mantovani A, Parmentier M, Facchetti F, Sozzani S. J Exp Med. 2005 Feb 21;201(4):509-15. doi: 10.1084/jem.20041310.

Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. Migeotte I, Riboldi E, Franssen JD, Grégoire F, Loison C, Wittamer V, Detheux M, Robberecht P, Costagliola S, Vassart G, Sozzani S, Parmentier M, Communi D. J Exp Med. 2005 Jan 3;201(1):83-93. doi: 10.1084/jem.20041277. Epub 2004 Dec 28.

The C-terminal nonapeptide of mature chemerin activates the chemerin receptor with low nanomolar potency. Wittamer V, Grégoire F, Robberecht P, Vassart G, Communi D, Parmentier M. J Biol Chem. 2004 Mar 12;279(11):9956-62. doi: 10.1074/jbc.M313016200. Epub 2003 Dec 29.

Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brézillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D. J Exp Med. 2003 Oct 6;198(7):977-85. doi: 10.1084/jem.20030382.

Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Blanpain C, Vanderwinden JM, Cihak J, Wittamer V, Le Poul E, Issafras H, Stangassinger M, Vassart G, Marullo S, Schlndorff D, Parmentier M, Mack M. Mol Biol Cell. 2002 Feb;13(2):723-37. doi: 10.1091/mbc.01-03-0129.

Structural and functional analysis of the RANTES-glycosaminoglycans interactions. Martin L, Blanpain C, Garnier P, Wittamer V, Parmentier M, Vita C. Biochemistry. 2001 May 29;40(21):6303-18. doi: 10.1021/bi002670n.

Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. Blanpain C, Wittamer V, Vanderwinden JM, Boom A, Renneboog B, Lee B, Le Poul E, El Asmar L, Govaerts C, Vassart G, Doms RW, Parmentier M. J Biol Chem. 2001 Jun 29;276(26):23795-804. doi: 10.1074/jbc.M100583200. Epub 2001 Apr 25.

Multiple nonfunctional alleles of CCR5 are frequent in various human populations. Blanpain C, Lee B, Tackoen M, Puffer B, Boom A, Libert F, Sharron M, Wittamer V, Vassart G, Doms RW, Parmentier M. Blood. 2000 Sep 1;96(5):1638-45.