Our research
The group of Marc Parmentier is dedicated to the study of G protein-coupled receptors, particularly the characterization of new receptors and their ligands (“deorphanization”). G protein-coupled receptors (GPCR) represent the largest family among membrane receptors. They play a major role in a variety of physiological and pathophysiological processes, and constitute the targets for almost half the active compounds presently used as therapeutic agents. The objective of our group is to characterize novel signalling pathways involving GPCRs, determine their contribution to physiology, and their involvement in diseases. We focus on receptors expressed in the brain or the immune system.
More than hundred GPCRs are still orphan, meaning that they have no known ligand, and often no known biological function. We search for natural ligands of orphan receptors starting from natural sources, such as tissue extracts and biological fluids. Orphan receptors are expressed in cell lines amenable for fast screening of biological activities. When activities are identified, the bioactive compounds are purified and characterized. Such characterization usually opens a new chapter of physiology. Our group has over the years characterized over a dozen receptors, including the thyrotropin receptor, adenosine receptors, chemokine and chemoattractant receptors, and receptors for neuropeptides, such as nociceptin, kisspeptins and prolactin-releasing peptide. The function of receptors in physiological processes and diseases is analyzed by the use of transgenic and knock out mouse lines, as well as similar models in zebrafish.
Group members
Marc Parmentier
Principal Investigator
(mparment@ulb.ac.be@ulb.ac.be)
phone # +32(0)2 555 4171
PhD students
KAAFARANI Abeer
Technicians
Radi Ayoub
Publications
Selected publications
Degroot GN, Lepage V, Parmentier M, Springael JY. The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking. Cells. 2022 Mar 18;11(6):1037. doi: 10.3390/cells11061037. PMID: 35326488; PMCID: PMC8947326.
Ben Dhaou C, Del Prete A, Sozzani S, Parmentier M. CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development. Front Cell Dev Biol. 2021 Dec 23;9:808455. doi: 10.3389/fcell.2021.808455. PMID: 35004698; PMCID: PMC8733553.
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. Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis. Cancers (Basel). 2021 Oct 5;13(19):5000. doi: 10.3390/cancers13195000. PMID: 34638484; PMCID: PMC8508266.
Dubois-Vedrenne I, Al Delbany D, De Henau O, Robert V, Vernimmen M, Langa F, Lefort A, Libert F, Wittamer V, Parmentier M. The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis. Oncotarget. 2021 Sep 14;12(19):1903-1919. doi: 10.18632/oncotarget.28056. PMID: 34548907; PMCID: PMC8448509.
Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Southan C, Davies JA, Abbracchio MP, Alexander W, Al-Hosaini K, Bäck M, Barnes NM, Bathgate R, Beaulieu JM, Bernstein KE, Bettler B, Birdsall NJM, Blaho V, Boulay F, Bousquet C, Bräuner-Osborne H, Burnstock G, Caló G, Castaño JP, Catt KJ, Ceruti S, Chazot P, Chiang N, Chini B, Chun J, Cianciulli A, Civelli O, Clapp LH, Couture R, Csaba Z, Dahlgren C, Dent G, Singh KD, Douglas SD, Dournaud P, Eguchi S, Escher E, Filardo EJ, Fong T, Fumagalli M, Gainetdinov RR, Gasparo M, Gerard C, Gershengorn M, Gobeil F, Goodfriend TL, Goudet C, Gregory KJ, Gundlach AL, Hamann J, Hanson J, Hauger RL, Hay DL, Heinemann A, Hollenberg MD, Holliday ND, Horiuchi M, Hoyer D, Hunyady L, Husain A, IJzerman AP, Inagami T, Jacobson KA, Jensen RT, Jockers R, Jonnalagadda D, Karnik S, Kaupmann K, Kemp J, Kennedy C, Kihara Y, Kitazawa T, Kozielewicz P, Kreienkamp HJ, Kukkonen JP, Langenhan T, Leach K, Lecca D, Lee JD, Leeman SE, Leprince J, Li XX, Williams TL, Lolait SJ, Lupp A, Macrae R, Maguire J, Mazella J, McArdle CA, Melmed S, Michel MC, Miller LJ, Mitolo V, Mouillac B, Müller CE, Murphy P, Nahon JL, Ngo T, Norel X, Nyimanu D, O’Carroll AM, Offermanns S, Panaro MA, Parmentier M, Pertwee RG, Pin JP, Prossnitz ER, Quinn M, Ramachandran R, Ray M, Reinscheid RK, Rondard P, Rovati GE, Ruzza C, Sanger GJ, Schöneberg T, Schulte G, Schulz S, Segaloff DL, Serhan CN, Stoddart LA, Sugimoto Y, Summers R, Tan VP, Thal D, Thomas WW, Timmermans PBMWM, Tirupula K, Tulipano G, Unal H, Unger T, Valant C, Vanderheyden P, Vaudry D, Vaudry H, Vilardaga JP, Walker CS, Wang JM, Ward DT, Wester HJ, Willars GB, Woodruff TM, Yao C, Ye RD. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein- coupled receptors. Br J Pharmacol. 2021 Oct;178 Suppl 1:S27-S156. doi: 10.1111/bph.15538. PMID: 34529832.
Ben Dhaou C, Mandi K, Frye M, Acheampong A, Radi A, De Becker B, Antoine M, Baeyens N, Wittamer V, Parmentier M. Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization. Angiogenesis. 2022 May;25(2):159-179. doi: 10.1007/s10456-021-09818-1. Epub 2021 Sep 15. PMID: 34524600.
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. Corrigendum: Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis. Front Oncol. 2020 Jun 23;10:977. doi: 10.3389/fonc.2020.00977. Erratum for: Front Oncol. 2019 Nov 15;9:1253. PMID: 32656083; PMCID: PMC7325103.
Mcheik S, Van Eeckhout N, De Poorter C, Galés C, Parmentier M, Springael JY. Coexpression of CCR7 and CXCR4 During B Cell Development Controls CXCR4 Responsiveness and Bone Marrow Homing. Front Immunol. 2019 Dec 18;10:2970. doi: 10.3389/fimmu.2019.02970. PMID: 31921208; PMCID: PMC6930800.
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. Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis. Front Oncol. 2019 Nov 15;9:1253. doi: 10.3389/fonc.2019.01253. Erratum in: Front Oncol. 2020 Jun 23;10:977. PMID: 31803622; PMCID: PMC6873210.
Peyrassol X, Laeremans T, Lahura V, Debulpaep M, El Hassan H, Steyaert J, Parmentier M, Langer I. Development by Genetic Immunization of Monovalent Antibodies Against Human Vasoactive Intestinal Peptide Receptor 1 (VPAC1), New Innovative, and Versatile Tools to Study VPAC1 Receptor Function. Front Endocrinol (Lausanne). 2018 Apr 5;9:153. doi: 10.3389/fendo.2018.00153. PMID: 29674997; PMCID: PMC5895782.
Ayoub MA, Crépieux P, Koglin M, Parmentier M, Pin JP, Poupon A, Reiter E, Smit M, Steyaert J, Watier H, Wilkinson T. Antibodies targeting G protein- coupled receptors: Recent advances and therapeutic challenges. MAbs. 2017 Jul;9(5):735-741. doi: 10.1080/19420862.2017.1325052. Epub 2017 May 5. PMID: 28475474; PMCID: PMC5524162.
Janssens R, Mortier A, Boff D, Ruytinx P, Gouwy M, Vantilt B, Larsen O, Daugvilaite V, Rosenkilde MM, Parmentier M, Noppen S, Liekens S, Van Damme J, Struyf S, Teixeira MM, Amaral FA, Proost P. Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes. Biochem Pharmacol. 2017 May 15;132:92-101. doi: 10.1016/j.bcp.2017.03.009. Epub 2017 Mar 18. PMID: 28322746.
Corbisier J, Huszagh A, Galés C, Parmentier M, Springael JY (2017). Partial Agonist and Biased Signaling Properties of the Synthetic Enantiomers J113863/UCB35625 at Chemokine Receptors CCR2 and CCR5. J Biol Chem 292:575-584.
De Henau O, Degroot GN, Imbault V, Robert V, De Poorter C, Mcheik S, Galés C, Parmentier M, Springael JY (2016). Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PLoS One 11:e0164179.
Peyrassol X, Laeremans T, Gouwy M, Lahura V, Debulpaep M, Van Damme J, Steyaert J, Parmentier M, Langer I (2016). Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor. J Immunol 196:2893-2901.
Corbisier J, Galès C, Huszagh A, Parmentier M, Springael JY (2015). Biased signaling at chemokine receptors. J Biol Chem 290:9542-9554.
Rouger L, Denis R, Luangsay S, Parmentier M (2013). ChemR23 knockout mice display mild obesity but no deficit in adipocyte differentiation. J Endocrinol 219:279-289.
Bondue B, Vosters O, De Nadai P, Glineur S, De Henau O, Luangsay S, Van Gool F, Communi D, De Vuyst P, Desmecht D, Parmentier M (2011). ChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia1. PLOS Pathogens, 7: e1002358.
Devosse D, Dutoit R, Migeotte I, Imbault V, Communi D, Salmon I, Parmentier M (2011). Processing of HEBP1 by cathepsin D gives rise to F2L, the agonist of Formyl Peptide Receptor 3. J Immunol 187:1475-1485.
Sohy D, Yano H, de Nadai P, Urizar E, Guillabert A, Javitch JA, Parmentier M, Springael JY (2009). Hetero-oligomerization of CCR2, CCR5 and CXCR4 and the protean effects of “selective”-antagonists. J Biol Chem 284:31270-31279.
Luangsay S, Wittamer V, Bondue B, De Henau O, Rouger L, Brait M, Franssen JD, de Nadai P, HuauxF, Parmentier M (2009). Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. J Immunol 183: 6489-6499.
Devosse T, Guillabert A, D’Haene N, Berton A, De Nadai P, Noel S, Brait M, Franssen JD, Sozzani S, Salmon I, Parmentier M (2009). Formyl peptide receptor-like 2 is expressed and functional in plasmacytoid dendritic cells, tissue-specific macrophage subpopulations, and eosinophils. J Immunol 182:4974-4984.
Sohy D, Parmentier M, Springael JY (2007). Allosteric trans-inhibition by specific antagonists in CCR2/CXCR4 heterodimers. J Biol Chem 282:30062-30069.
Springael JY, Nguyen PL, Urizar E, Costagliola S, Vassart G, Parmentier M (2006). Allosteric modulation of binding properties between units of chemokine receptor homo- and hetero-oligomers. Mol Pharmacol. 69:1652-1661.
Laurent P, Becker JAJ, Valverde O, Ledent C, de Kerchove d’Exaerde A, Schiffmann SN, Maldonado R, Vassart G and Parmentier M (2005). The prolactin-releasing peptide acts as a functional antagonist of the opioid system through its receptor GPR10. Nature Neurosciences, 8:1735-1741.
Migeotte I, Riboldi E, Franssen JD, Gregoire F, Loison C, Wittamer V, Detheux M, Robberecht P, Costagliola S, Vassart G, Sozzani S, Parmentier M, Communi D (2005). Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. J Exp Med. 201:83-93.
El-Asmar L, Springael JY, Ballet S, Urizar Andrieu E, Vassart G, Parmentier M (2005). Evidence for negative binding cooperativity within CCR5-CCR2b heterodimers. Mol Pharmacol. 67:460-469
Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brezillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D (2003). Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med. 198: 977-985.
Blanpain C, Vanderwinden JM, Cihak J, Wittamer V, Le Poul E, Issafras H, Stangassinger M, Vassart G, Marullo S, Schlondorff D, Parmentier M, Mack M (2002). Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Mol Biol Cell 13: 723-737.
Detheux M, Standker L, Vakili J, Munch J, Forssmann U, Adermann K, Pohlmann S, Vassart G, Kirchhoff F, Parmentier M and Forssmann WG (2000). Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties. J. Exp. Med. 192: 1501-1508.
Blanpain C, Lee B, Tackoen M, Puffer B, Boom A, Libert F, Sharron M, Wittamer V, Vassart G, Doms RW, Parmentier M (2000). Multiple nonfunctional alleles of CCR5 are frequent in various human populations. Blood 96: 1638-1645.
Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, Vassart G, Doms RW and Parmentier M (1999). CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood 94 1899-1905.
Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Böhme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999). Unresponsiveness to Cannabinoids and Reduced Addictive Effects of Opiates in CB1 Receptor Knock Out Mice. Science 285: 401-404.
Schurmans S, Schiffmann SN, Gurden H, Lemaire M, Lipp HP, Schwam V, Pochet R, Imperato A, Böhme GA and Parmentier M (1997). Impaired regional LTP in calretinin-deficient mice. Proc. Natl. Acad. Sci. USA 94: 10415-10420.
Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G and Parmentier M (1997). Aggressiveness, hypoalgesia and increased blood pressure in mice deficient for the adenosine A2a receptor. Nature 388: 674-678.
Rucker J, Samson M, Doranz BJ, Libert F, Berson JF, Yi Y, Collman RG, Broder CC, Vassart G, Doms RW and Parmentier M (1996). Regions in -Chemokine Receptors CCR5 and CCR2b that Determine HIV-1 Cofactor Specificity. Cell 87: 437-446.
Mollereau C, Simons MJ, Soularue P, Liners F, Vassart G Meunier JC and Parmentier M (1996). Structure, tissue distribution and chromosomal localization of the prepronociceptin gene. Proc. Natl. Acad. Sci. USA 93: 8666-8670.
Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapouméroulie C, Cogniaux J, Forceille C, Muyldermans G, Verhofstede C, Guy Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G and Parmentier M (1996). Resistance to HIV-1 infection of Caucasian individuals bearing mutant alleles of the CCR5 chemokine receptor gene. Nature 382: 722-725.
Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Parmentier M, Collman RG, and Doms RW (1996). A dual-tropic, primary HIV-1 isolate that uses both fusin and the -chemokine receptor CKR-5 as entry cofactors. Cell 85: 1149-1158.
Samson M, Labbé O, Mollereau C, Vassart G and Parmentier M (1996). Molecular cloning and functional characterization of a new CC-chemokine receptor gene. Biochemistry 35: 3362-3367.
Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot C, Ferrara P, Monsarrat B, Mazarguil H, Vassart G, Parmentier M and Costentin J (1995). Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377: 532-535.
Vanderhaeghen P, Schurmans S, Vassart G and Parmentier M (1993). Olfactory receptors are displayed on dog mature sperm cells. J. Cell Biol. 123 : 1441-1452.
Parmentier M, Libert F, Schurmans, S., Shiffmann S, Lefort A, Eggerickx D, Ledent C, Mollereau C, Gérard C, Perret J, Grootegoed JA, and Vassart G (1992). Expression of members of the putative olfactory receptor gene family in mammalian germ cells. Nature 355: 453-455.
Ledent C, Dumont JE, Vassart G, and Parmentier M (1992). Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism. EMBO J. 11: 537-542.
Ledent C, Parmentier M, and Vassart G (1990). Tissue specific expression and methylation of a thyroglobulin-CAT gene in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 87: 6176-6180.
Parmentier M, Libert F, Maenhaut C, Lefort A, Gérard C, Perret J, Van Sande J, Dumont JE and Vassart G (1989). Molecular cloning of the thyrotropin receptor. Science 246: 1620-1622.
Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ. Dumont JE and Vassart G (1989). Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244: 569-572.