Gilbert VASSART group

PEOPLE

 


Marie-Isabelle Garcia: Senior post-doctoral position

She performed her PhD in Biochemistry at the University Paris VII (France) in 1996 and pursued with a postodoctoral position at the Institut Pasteur (France) where she studied the role of cell adhesion as a virulence factor in the infectious process of pathogenic E. coli strains. She performed a postdoctoral training at the University La Sapienza of Rome (Italy) to study the role of the major capsid protein VP1 from Polyomavirus in the early stages of infection and host specificity (1998-2004). She joined the ULB laboratory in 2006 as a postdoctoral fellow to study Lgr receptors.

 

 

Gilbert Vassart: Principal Investigator


Gilbert Vassart pioneered the use of molecular genetics approaches to solve endocrinology issues. Over the past three decades, together with his collaborators, he cloned genes involved in thyroid hormone production and identified the first mutations responsible for congenital hypothyroidism in man and animal models. In 1989, as a “side product” of TSH receptor cloning he cloned a host of G protein-coupled receptors (GPCRs), opening the way to the identification of known and orphan receptors by reverse pharmacology. In collaboration with Marc Parmentier, this led to the deorphanization of several GPCRs, including CCR5, and to the identification of the delta32 mutation conferring resistance to infection by HIV1. Concentrating on the glycoprotein hormone receptor subfamily, he identified the first natural gain of function mutations in the TSH receptor responsible for autonomous toxic thyroid adenomas or hereditary non-autoimmune hyperthyroidism, and the first mutations causing broadening of the specificity of the FSH receptor, causing spontaneous ovarian hyperstimulation syndrome.

 

 

Selection of major publications (> 21,000 citations)


Vassart, G., S. Refetoff, H. Brocas, C. Dinsart, and J.E. Dumont (1975). Translation of thyroglobulin 33S messenger RNA as a means of determining thyroglobulin quaternary structure. Proc.Natl.Acad.Sci.U.S.A. 72:3839-3843.

Mercken, L., M.J. Simons, S. Swillens, M. Massaer, and G. Vassart (1985). Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature 316:647-651.

Ricketts, M.H., V. Pohl, G. de Martynoff, C.D. Boyd, A.J. Bester, P.P. Van Jaarsveld, and G. Vassart (1985). Defective splicing of thyroglobulin gene transcripts in the congenital goitre of the Afrikander cattle. EMBO J. 4:731-737.

Libert, F., J. Ruel, M. Ludgate, S. Swillens, N. Alexander, G. Vassart, and C. Dinsart (1987). Thyroperoxidase, an auto-antigen with a mosaic structure made of nuclear and mitochondrial gene modules. EMBO J. 6:4193-4196.

Vassart G, Georges M, Monsieur R, Brocas H, Lequarre AS, Christophe D (1987). A sequence in M13 phage detects hypervariable minisatellites in human and animal DNA. Science 235:683-4. Libert, F., M. Parmentier, A. Lefort, C. Dinsart, J. Van Sande, C. Maenhaut, M.J. Simons, J.E. Dumont, and G. Vassart (1989). Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244:569-572.

Libert, F., S.N. Schiffmann, A. Lefort, M. Parmentier, C. Gerard, J.E. Dumont, J.J. Vanderhaeghen, and G. Vassart (1991). The orphan receptor cDNA RDC7 encodes an A1 adenosine receptor. EMBO J. 10:1677-1682.

Ieiri, T., P. Cochaux, H. Targovnik, M. Suzuki, S.I. Shimoda, J. Perret, and G. Vassart (1991). A 3' splice site mutation in the thyroglobulin gene responsible for congenital goitre with hypothyroidism. J.Clin.Invest. 88:1901-1905.

Abramowicz, M.J., H.M. Targovnik, V. Varela, P. Cochaux, L. Krawiec, M.A. Pisarev, F.V.E. Propato, G. Juvenal, H.A. Chester, and G. Vassart (1992). Identification of a mutation in the coding sequence of the human thyroid peroxidase gene causing congenital goiter. J.Clin.Invest. 90:1200-1204.

Parmentier, M., F. Libert, S. Schurmans, S. Schiffmann, A. Lefort, D. Eggerickx, C. Ledent, C. Mollereau, C. Gerard, J. Perret, A. Grootegoed, and G. Vassart (1992). Expression of members of the putative olfactory receptor gene family in mammalian germ cells. Nature 355:453-455.

Parma, J., L. Duprez, J. Van Sande, P. Cochaux, C. Gervy-Decoster, J. Mockel, J.E. Dumont, and G. Vassart (1993). Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649-651.

Duprez, L., J. Parma, J. Van Sande, A. Alleier, J. Leclère, C. Schvartz, M.-J. Delisle, M. Decoulx, J. Orgiazzi, J.E. Dumont, and G. Vassart (1994). Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat.Genet. 7:396-401.

Kopp, P., J. Van Sande, J. Parma, L. Duprez, H. Gerber, E. Joss, L. Jameson, J.E. Dumont, and G. Vassart (1995). Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin receptor gene. N.Engl.J.Med. 19:150-154.

Samson, M., F. Libert, B.J. Doranz, J. Rucker, C. Liesnard, C.M. Farber, S. Saragosti, C. Lapouméroulie, J. Cognaux, C. Forceille, G. Muyldermans, C. Verhofstede, G. Burtonboy, M. Georges, T. Imai, S. Rana, Y. Yi, R.J. Smyth, R.G. Collman, R.W. Doms, G. Vassart, and M. Parmentier (1996). Resistance to HIV-1 infecton in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722-725.

Abramowicz, M.J., L. Duprez, J. Parma, G. Vassart, and C. Heinrichs (1997). Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J.Clin.Invest. 99:3018-3024.

Ledent, C., J.M. Vaugeois, S.N. Schiffmann, T. Pedrazzini, M. El yacoubi, J.J. Vanderhaeghen, J. Costentin, J.K. Heath, G. Vassart, and M. Parmentier (1997). Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature 388:674-678.

Rodien, P., C. Brémont, ML. Raffin, J. Parma, J. Van Sande, S. Costagliola, JP. luton, G. Vassart, and L. Duprez (1998). Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N.Engl.J.Med. 339:1823-1826.

Smits G, Olatunbosun O, Delbaere A, Pierson R, Vassart G, Costagliola S (2003). Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N Engl J Med 349:760-6.

Smits G, Campillo M, Govaerts C, Janssens V, Richter C, Vassart G, Pardo L, Costagliola S (2003). Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity. EMBO J 22:2692-703.

Laurent P, Becker JA, Valverde O, Ledent C, de Kerchove d'Exaerde A, Schiffmann SN, Maldonado R, Vassart G, Parmentier M (2005). The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10. Nat Neurosciences 8:1735-41.

Ledent C, Demeestere I, Blum D, Petermans J, Hamalainen T, Smits G, Vassart G (2005). Premature ovarian aging in mice deficient for Gpr3. Proc Natl Acad Sci USA 102:8922-6. Urizar E, Montanelli L, Loy T, Bonomi M, Swillens S, Gales C, Bouvier M, Smits G, Vassart G, Costagliola S (2005). Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity. EMBO J 24:1954-64.

Decaux G, Soupart A, Vassart G Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet. 2008 May 10;371(9624):1624-32. Garcia MI, Ghiani M, Lefort A, Libert F, Strollo S, Vassart G. (2009) LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine. Dev Biol  331(1):58-67

Mustata RC, Van Loy T, Lefort A, Libert F, Strollo S, Vassart G, Garcia MI (2011). Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo. EMBO Rep. 12(6):558-64. Vassart G, Costagliola S. G protein-coupled receptors: mutations and endocrine diseases (2011). Nat Rev Endocrinol. 7(6):362-72.

Zoenen M, Urizar E, Swillens S, Vassart G, Costagliola S. Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers. (2012) Nat Commun. 2012;3:1007.

 

 

 

 

Valeria Fernandez-Vallone: Post-doctoral position

 

 

She performed her PhD in Biochemistry at the University of Buenos Aires (Argentina) in 2012 where she studied the importance of bone marrow mesenchymal stem cells in the regulation of the osteogenesis, osteoclastogenesis and bone resorption in breast cancer patients. She joined our lab in August 2012 to study the in vivo function of Lgr receptors. She has characterized intestinal and gastric fetal progenitors and regenerating cells in the mouse adult gastric epithelium.

 

 

 

 

 

Morgane Leprovots:Technician

 

 

She obtained a Bachelor degree in Cellular biology, genetics, microbiology and physiology in 2011 at the University of Rennes (France) and a vocational bachelor in Biology in 2012 at the IUT Tours (France). She joined our lab in September 2013.

 

 

Romain Gerbier: postdoctoral position

 

He obtained his PhD in Cellular Pharmacology in 2011 working on the role of central neuropeptides in regulation of body fluid homeostasis and cardiovascular functions (College de France, France). He performed postdoctoral research experiences on development of metabolically stable apelin analogs (College de France, 2011-2013) and on the in vivo characterization of mouse MTR/5-HT2c heteromerization (Institut Cochin, France, 2013-2016). He has joined the group in october 2016 to study Lgr receptors biology.

 

 

 

Alumni

 

Gabriela Vasile: she participated to the characterization of murine fetal progenitors (2011-2015).

 

Sofia Cheyroux: she studied the ex vivo function of particular GPCRs in intestinal progenitors and adult stem cells as a trainee (Feb-Aug. 2015).


Roxana Mustata: postdoctoral position from 2009 to 2012. She studied the role of the Lgr4 receptor in murine intestinal stem cells and characterized murine fetal intestinal progenitors.

 

Tom Van Loy: postdoctoral position from 2009 to 2011. He worked on Lgr de-orphanization and participated to the study of the role of the Lgr4 receptor in murine intestinal stem cells. He also contributed to de-orphanization of the Drosophila ortholog Lgr2 ligand (Bursicon).

 

Maria-Angela Ghiani: medical doctor trainee in molecular biology from 2006 to 2007. She studied the role of Lgr5 receptor during murine intestinal development.

 

Fernando Mendive: postdoctoral position from 2002 to 2006. He worked on Lgr structure-function and on the role of Lgr4 in male fertility. He also contributed to de-orphanization of the Drosophila ortholog Lgr2 ligand (Bursicon).

 

Gregory Van Schoore: Obtained his PhD in 2008 where he defined the distribution of the Lgr4 receptor in the mouse tissues and he contributed to the study of the role of Lgr4 in male fertility.

 

Sylvie Claeysen: postdoctoral position from 2000 to 2002. She started the study of Lgrs in our lab.

 

 

 

 

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