Sabine Costagliola

Our research

https://costalab.ulb.ac.be

ES cells and zebrafish to study thyroid development and thyroid disease

The main research focus of our team is the molecular dissection of the signaling mechanisms and gene networks involved in thyroid organogenesis and thyroid diseases (congenital hupothyroidism and thyroid cancer). To date, the signaling mechanisms that control the specification of endoderm-derived organs such as the thyroid, lung, liver or pancreas remain poorly understood. To tackle the question “how different cell types are specified from the gut endoderm?”,  we use the thyroid as experimental model. Thyroid organogenesis can be grossly divided into 3 phases comprising (a) thyroid precursor cell specification, (b) budding and migration of the thyroid primordium, and (c) functional differentiation of thyroid follicular cells. While some factors critical for migration, differentiation and growth of the thyroid primordium have been identified in mouse knock-out models, little is known about the molecular events involved in thyroid precursors cell specification.

Our working strategy aims to merge data obtained with two different experimental models – Thyroid cells differentiated in vitro from genetically modified ES cells and zebrafish – to elucidate the genetic basis of thyroid development, the molecular basis of thyroid cell differentiation and thyroid cancer initiation and progression.

Based on data obtained from global expression analysis of normal thyroid development In vitro or in zebrafish as well as from models of thyroid dysgenesis and thyroid cancer, a reverse genetic approach is applied by using CRISPR/Cas for creating knockout alleles of candidate genes in ES cells and zebrafish.

This will help:
-to offer new diagnostic targets (=new candidates genes) to patients with thyroid dysgenesis.
-to identify (i) the developmental thyroid tempo orchestrated by some signaling pathways controlled by the cardio vascular system which (ii) would help to build in vitro models where thyroid differentiation could be trigger by chemically defined culture conditions and in absence of any genetic manipulation. This last achievement would pave the way for a human model of in vitro thyroid differentiation and could offer unprecedented therapeutic options to patients with thyroid dysgenesis or medical thyroid ablation.
-to Identify the early events that contribute to thyroid cancer initiation and/or progression

Zebrafish models of centronuclear myopathies

Centronuclear myopathies (CNM) are the third most common type of congenital myopathies. They are characterized histologically by an increased number of centrally localized nuclei in atrophic muscle fibers. CNM can be caused by mutations in several genes: autosomal dominant mutations in the DNM2 gene coding for dynamin 2, autosomal recessive mutations in the BIN1 gene coding for amphiphysin 2 and X-linked recessive mutations in the MTM1 gene coding for myotubularin causing X-linked centronuclear myopathy.

The project aims at understanding the molecular interactions between myotubularin, amphiphysin and dynamin that are implicated in the physiopathology of centronuclear myopathies and myotonic dystrophies. These proteins are implicated in membrane trafficking and T-tubule biogenesis. Dynamin 2 levels are increased in patients with myotubular myopathy and downregulation of dynamin 2 in MTM1 KO mouse alleviates the phenotype.

Zebrafish larvae is a highly efficient tool to model muscle diseases. With the availability of large clutches size, the model allows efficient chemical screens by simply adding drugs to the water. Zebrafish could therefore be an excellent model to test the efficacy of different concentrations of dynamin 2 inhibitors.

Our second aim is to Identify the genetic causes of congenital myopathies in patients without mutations in known candidate genes. Through collaborations with several neuromuscular reference centers in Belgium, we are using an integrated approach combining a comprehensive phenotypic analysis, exome sequencing and zebrafish knock-outs to characterize in vivo new genetic variants with zebrafish lines created “à la carte”.

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Group members

Sabine Costagliola, PI, Senior Research Associate FNRS (scostag@ulb.ac.be)
IRIBHM vice director

phone # +32(0)2 555 6085

Sabine Costagliola completed a PhD in immunology at the Université Aix Marseille II (France) in 1991 and a PhD in Biomedical Science at ULB in 2000.  She obtained a permanent position at FNRS as Research Associate in 2000.  She is group leader and vice director of IRIBHM (Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire).

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Lab Manager :

Véronique Janssens

(verojans@ulb.ac.be
phone # +32(0)2 555 4197

Véronique studied at the “Athénée des Pagodes” obtained her CESS (option Latin – math) in 1994. She followed the first year of pharmacology at the “Université Libre de Bruxelles” (ULB). From 1995 to 1998, she performed a graduate in Medical Biology in “Institute Paul Lambin” (UCL) (assay: “Huntington chorea”) and obtained her diploma as technician of laboratories. In 1998, she started to work in Sabine Costagliola lab as lab technician and she obtained a permanent position at ULB in 2003. In 2013, she obtained a career advancement at ULB after a competitive examination and an essay entitled : “Zebrafish: a new biomedical research tool at ULB?”. Véronique is our lab manager.

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Postdocs :

Bárbara Fonseca
Bárbara Fonseca graduated in Biomedical Sciences at Fluminense Federal University (2010), followed by a Master’s degree in Cell and Developmental Biology at Federal University of Rio de Janeiro (2013), both in Brazil. She obtained a Ph.D. degree in Cell and Developmental Biology in 2017, at Pierre et Marie Curie University, in Paris (France). Currently, she is a postdoctoral researcher at IRIBHM-ULB, working on in vitro models of thyroid development.

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Olivier Monestier
Olivier Monestier completed his PhD in genomics and molecular genetics at the University of Limoges in 2012, under the supervision of Professor Véronique Blanquet (Animal Molecular Genetics Unit, Limoges, France). During his thesis, he developed and characterized mouse models associated with hypermuscular phenotype, notably some lines overexpressing the WFIKKN2 gene. From 2012 to 2015, he worked on the function and molecular evolution of TGFB proteins implicated in mammal reproduction as a postdoctoral researcher at the GenPhySE laboratory in the French National Institute for Agricultural Research (INRA) center of Toulouse (France) and then, as a research and teaching assistant at the University of Limoges. From 2015 to 2017, he worked on the molecular mechanisms of muscle stem cells fusion in fish as a postdoctoral researcher at the Fish Physiology and Genomics Institute in the Growth and Flesh Quality group lead by Jean-Charles Gabillard. Since 2017, he has been a postdoctoral researcher at the IRIBHM in the laboratory of Sabine Costagliola working on the generation of in vitro models of thyroid cancer.

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Mírian Romitti

Graduated in Biomedical Sciences from University of Cruz Alta, Brazil, 2008. Master (2012) and PhD (2014) in Biomedical Sciences: Endocrinology from University Federal of Rio Grande do Sul, Brazil. Postdoctoral researcher at Sabine Costagliola´s Lab, IRIBHM, ULB, Belgium from 2014 to 2017. Currently Chargé de Recherche FNRS.

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PhD Students:

Sandra Coppens
MD, specialization in neurology (2011), in pediatric neurology (2013) at ULB.  Interuniversity degree in myology in 2013 (Paris-Descartes University), interuniversity certificate in genetics in 2016 (Belgian Society of Human Genetics) Resident in pediatric neurology and pediatric consultations at the Neuromuscular Reference Center at Hospital Erasme and HUDERF from 2013 to 2017. PhD student at IRIBHM since 2015 (funded by the Fond Erasme and the Belgian Kids Fund). Title of the PhD thesis: Identification of genetic causes of myopathies through an integrated approach to in-depth phenotypic analysis, exome sequencing and gene knockdown in zebrafish

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Eleonore Dupuis
Eleonore joined IRIBHM for a master thesis in September 2014 in Wittamer Lab. She graduated for her master in June 2015 and joined the Costagliola Lab for a PhD funded by the Belgian Kids Fund. Her research project focused on zebrafish models to study the molecular networks of the myotubularin / amphiphysin / dynamin pathway involved in centronuclear myopathies

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Pierre Gillotay
Pierre graduated from Lycée Henriette Dachsbeck in June 2010 with a “latin-science” formation. He entered ULB to study biomedical sciences in September 2010 and got his bachelor degree in June 2013. After starting a master’s degree in biomedical sciences in September 2013, he joined the lab for a master thesis in September 2014 working on the impact of vascular development in thyroid organogenesis. He graduated for his master in June 2015 and stayed in the lab for a PhD after getting a FRIA fellowship in October 2015. His current work in mainly focused on understanding the fine molecular tuning of thyroid organogenesis using the Crispr-Cas9 technology.

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Benoît Haerlingen

Benoit completed his bachelor degree in biomedical sciences at the University of Namur in 2010 and a master in cellular and molecular biology at the Free University of Brussels in 2012. Since October 2012 he is PhD student in Costagliola lab and his research project focuses on cellular interactions between the thyroid and the heart in the developing embryo.

 

 

 

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Benjamin Dassy- Master student

 

Graduated in 2014 with a « latin sciences » degree from Athenée Bracops-Lambert, Benjamin started a bachelor in biomedical sciences at the “Université Libre de Bruxelles” (ULB). After a nice internship, he joined the team for a master thesis. He’s currently working with Pierre Gillotay on the thyroid development.

 

Publications

[1] A. Trubiroha, P. Gillotay, N. Giusti, D. Gacquer, F. Libert, A. Lefort, B. Haerlingen, X. Deken, R. Opitz, and S. Costagliola, “A Rapid CRISPR/Cas-based Mutagenesis Assay in Zebrafish for Identification of Genes Involved in Thyroid Morphogenesis and Function,” Sci. Rep., pp. 1–19, Mar. 2018.
[2] F. Antonica, D. F. Kasprzyk, A. A. Schiavo, M. Romitti, and S. Costagliola, “Generation of Functional Thyroid Tissue Using 3D-Based Culture of Embryonic Stem Cells.,” Methods Mol Biol, vol. 1597, pp. 85–95, 2017.
[3] R. Opitz, M.-P. Hitz, I. Vandernoot, A. Trubiroha, R. Abu-Khudir, M. Samuels, V. Désilets, S. Costagliola, G. Andelfinger, and J. Deladoëy, “Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis.,” Endocrinology, vol. 156, no. 1, pp. 377–388, Jan. 2015.
[4] R. Opitz, F. Antonica, and S. Costagliola, “New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox,” European Thyroid Journal, vol. 2, no. 4, pp. 229–242, 2013.
[5] R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Dev Biol, vol. 372, no. 2, pp. 203–216, Dec. 2012.
[6] F. Antonica, D. F. Kasprzyk, R. Opitz, M. Iacovino, X.-H. Liao, A. M. Dumitrescu, S. Refetoff, K. Peremans, M. Manto, M. Kyba, and S. Costagliola, “Generation of functional thyroid from embryonic stem cells,” Nature, vol. 491, no. 7422, pp. 66–71, Nov. 2012.
[7] Rodriguez, Jin, V. Janssens, Pierreux, Hick, E. Urizar, and S. Costagliola, “Deletion of the RNaseIII Enzyme Dicer in Thyroid Follicular Cells Causes Hypothyroidism with Signs of Neoplastic Alterations,” PLoS ONE, vol. 7, no. 1, p. e29929, Jan. 2012.
[8] M. Zoenen, E. Urizar, S. Swillens, G. Vassart, and S. Costagliola, “Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers,” Nature Communications, vol. 3, pp. 985–9, 2012.
[9] R. Opitz, E. Maquet, M. Zoenen, R. Dadhich, and S. Costagliola, “TSH receptor function is required for normal thyroid differentiation in zebrafish.,” Mol Endocrinol, vol. 25, no. 9, pp. 1579–1599, Sep. 2011.
[10] G. Vassart and S. Costagliola, “G protein-coupled receptors: mutations and endocrine diseases.,” Nat Rev Endocrinol, vol. 7, no. 6, pp. 362–372, Jun. 2011.
[11] S. Costagliola, “Thyrotropin receptor activation by autoantibodies: A butterfly effect,” Ann Endocrinol (Paris), vol. 72, no. 2, pp. 114–116, Apr. 2011.
[12] D. Tiotiu, B. Alvaro Mercadal, R. Imbert, J. Verbist, I. Demeestere, A. De Leener, Y. Englert, G. Vassart, S. Costagliola, and A. Delbaere, “Variants of the BMP15 gene in a cohort of patients with premature ovarian failure,” Hum Reprod, vol. 25, no. 6, pp. 1581–1587, Jun. 2010.
[13] M. Dieterich, M. Bolz, T. Reimer, S. Costagliola, and B. Gerber, “Two different entities of spontaneous ovarian hyperstimulation in a woman with FSH receptor mutation,” Reproductive biomedicine online, pp. 1–8, Apr. 2010.
[14] E. Maquet, S. Costagliola, J. Parma, C. Christophe-Hobertus, L. L. Oligny, J.-C. Fournet, Y. Robitaille, J.-M. Vuissoz, A. Payot, S. Laberge, G. Vassart, G. Van Vliet, and J. Deladoëy, “Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene.,” J Clin Endocrinol Metab, vol. 94, no. 1, pp. 197–203, Jan. 2009.
[15] S. Akcurin, D. Turkkahraman, C. Tysoe, S. Ellard, A. De Leener, G. Vassart, and S. Costagliola, “A family with a novel TSH receptor activating germline mutation (p.Ala485Val).,” Eur. J. Pediatr., vol. 167, no. 11, pp. 1231–1237, Nov. 2008.
[16] G. Caltabiano, M. Campillo, A. De Leener, G. Smits, G. Vassart, S. Costagliola, and L. Pardo, “The specificity of binding of glycoprotein hormones to their receptors,” Cell Mol Life Sci, vol. 65, no. 16, pp. 2484–2492, Aug. 2008.
[17] J. H. D. Bassett, A. J. Williams, E. Murphy, A. Boyde, P. G. T. Howell, R. Swinhoe, M. Archanco, F. Flamant, J. Samarut, S. Costagliola, G. Vassart, R. E. Weiss, S. Refetoff, and G. R. Williams, “A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism.,” Mol Endocrinol, vol. 22, no. 2, pp. 501–512, Feb. 2008.
[18] A. De Leener, G. Caltabiano, S. Erkan, M. Idil, G. Vassart, L. Pardo, and S. Costagliola, “Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome.,” Hum. Mutat., vol. 29, no. 1, pp. 91–98, Jan. 2008.
[19] S. Costagliola and A. De Leener, “[Molecular mechanisms selected by evolution m primates for self-protection against human chorionic gonadotropin],” Bull Mem Acad R Med Belg, vol. 163, no. 10, pp. 481–4; discussion 484–5, 2008.
[20] J.-Y. Springael, E. Urizar, S. Costagliola, G. Vassart, and M. Parmentier, “Allosteric properties of G protein-coupled receptor oligomers.,” Pharmacol. Ther., vol. 115, no. 3, pp. 410–418, Sep. 2007.
[21] M. Bonomi, M. Busnelli, L. Persani, G. Vassart, and S. Costagliola, “Structural differences in the hinge region of the glycoprotein hormone receptors: evidence from the sulfated tyrosine residues.,” Mol Endocrinol, vol. 20, no. 12, pp. 3351–3363, Dec. 2006.
[22] A. Delbaere, G. Smits, G. Vassart, and S. Costagliola, “Genetic predictors of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization.,” Nat Clin Pract Endocrinol Metab, vol. 2, no. 11, pp. 590–591, Nov. 2006.
[23] J. Van Durme, F. Horn, S. Costagliola, G. Vriend, and G. Vassart, “GRIS: glycoprotein-hormone receptor information system.,” Mol Endocrinol, vol. 20, no. 9, pp. 2247–2255, Sep. 2006.
[24] J.-Y. Springael, P. N. Le Minh, E. Urizar, S. Costagliola, G. Vassart, and M. Parmentier, “Allosteric modulation of binding properties between units of chemokine receptor homo- and hetero-oligomers.,” Mol. Pharmacol., vol. 69, no. 5, pp. 1652–1661, May 2006.
[25] A. De Leener, L. Montanelli, J. Van Durme, H. Chae, G. Smits, G. Vassart, and S. Costagliola, “Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology,” J Clin Endocrinol Metab, vol. 91, no. 2, pp. 555–562, Feb. 2006.
[26] S. Costagliola, E. Urizar, F. Mendive, and G. Vassart, “Specificity and promiscuity of gonadotropin receptors.,” Reproduction, vol. 130, no. 3, pp. 275–281, Sep. 2005.
[27] A. Elgadi, C.-G. Arvidsson, A. Janson, C. Marcus, S. Costagliola, and S. Norgren, “Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.,” Acta Paediatr., vol. 94, no. 8, pp. 1145–1148, Aug. 2005.
[28] E. Urizar, L. Montanelli, T. Loy, M. Bonomi, S. Swillens, C. Gales, M. Bouvier, G. Smits, G. Vassart, and S. Costagliola, “Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity.,” EMBO J, vol. 24, no. 11, pp. 1954–1964, Jun. 2005.
[29] A. Boschi, C. Daumerie, M. Spiritus, C. Beguin, M. Senou, D. Yuksel, M. Duplicy, S. Costagliola, M. Ludgate, and M. C. Many, “Quantification of cells expressing the thyrotropin receptor in extraocular muscles in thyroid associated orbitopathy,” Br J Ophthalmol, vol. 89, no. 6, pp. 724–729, Jun. 2005.
[30] E. Urizar, S. Claeysen, X. Deupí, C. Govaerts, S. Costagliola, G. Vassart, and L. Pardo, “An activation switch in the rhodopsin family of G protein-coupled receptors: the thyrotropin receptor.,” J Biol Chem, vol. 280, no. 17, pp. 17135–17141, Apr. 2005.
[31] A. Delbaere, G. Smits, A. De Leener, S. Costagliola, and G. Vassart, “Understanding ovarian hyperstimulation syndrome.,” Endocrine, vol. 26, no. 3, pp. 285–290, Apr. 2005.
[32] I. Migeotte, E. Riboldi, J.-D. Franssen, F. Grégoire, C. Loison, V. Wittamer, M. Detheux, P. Robberecht, S. Costagliola, G. Vassart, S. Sozzani, M. Parmentier, and D. Communi, “Identification and characterization of an endogenous chemotactic ligand specific for FPRL2.,” J Exp Med, vol. 201, no. 1, pp. 83–93, Jan. 2005.
[33] C. Daelemans, G. Smits, V. de Maertelaer, S. Costagliola, Y. Englert, G. Vassart, and A. Delbaere, “Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism.,” J Clin Endocrinol Metab, vol. 89, no. 12, pp. 6310–6315, Dec. 2004.
[34] S. Costagliola, M. Bonomi, N. G. Morgenthaler, J. Van Durme, V. Panneels, S. Refetoff, and G. Vassart, “Delineation of the discontinuous-conformational epitope of a monoclonal antibody displaying full in vitro and in vivo thyrotropin activity.,” Mol Endocrinol, vol. 18, no. 12, pp. 3020–3034, Dec. 2004.
[35] M. Salek, S. Costagliola, and W. D. Lehmann, “Protein tyrosine-O-sulfation analysis by exhaustive product ion scanning with minimum collision offset in a NanoESI Q-TOF tandem mass spectrometer.,” Anal. Chem., vol. 76, no. 17, pp. 5136–5142, Sep. 2004.
[36] L. Meeus, B. Gilbert, C. Rydlewski, J. Parma, A. L. Roussie, M. Abramowicz, C. Vilain, D. Christophe, S. Costagliola, and G. Vassart, “Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid.,” J Clin Endocrinol Metab, vol. 89, no. 9, pp. 4285–4291, Sep. 2004.
[37] L. Montanelli, J. J. J. Van Durme, G. Smits, M. Bonomi, P. Rodien, E. J. Devor, K. Moffat-Wilson, L. Pardo, G. Vassart, and S. Costagliola, “Modulation of ligand selectivity associated with activation of the transmembrane region of the human follitropin receptor.,” Mol Endocrinol, vol. 18, no. 8, pp. 2061–2073, Aug. 2004.
[38] L. Montanelli, A. Delbaere, C. Di Carlo, C. Nappi, G. Smits, G. Vassart, and S. Costagliola, “A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.,” J Clin Endocrinol Metab, vol. 89, no. 4, pp. 1255–1258, Apr. 2004.
[39] M. J. Costa, Y. Song, P. Macours, C. Massart, M. C. Many, S. Costagliola, J. E. Dumont, J. Van Sande, and V. Vanvooren, “Sphingolipid-cholesterol domains (lipid rafts) in normal human and dog thyroid follicular cells are not involved in thyrotropin receptor signaling,” Endocrinology, vol. 145, no. 3, pp. 1464–1472, Mar. 2004.
[40] A. Delbaere, G. Smits, O. Olatunbosun, R. Pierson, G. Vassart, and S. Costagliola, “New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome?,” Hum Reprod, vol. 19, no. 3, pp. 486–489, Mar. 2004.
[41] G. Vassart, L. Pardo, and S. Costagliola, “A molecular dissection of the glycoprotein hormone receptors.,” Trends Biochem. Sci., vol. 29, no. 3, pp. 119–126, Mar. 2004.
[42] G. Vassart and S. Costagliola, “A physiological role for the posttranslational cleavage of the thyrotropin receptor?,” Endocrinology, vol. 145, no. 1, pp. 1–3, Jan. 2004.
[43] S. Costagliola, “[Structure-function relations of glycoprotein hormone receptors and their medical applications],” Bull Mem Acad R Med Belg, vol. 159, no. 5, pp. 367–375, 2004.
[44] J. Van Sande, M. J. Costa, C. Massart, S. Swillens, S. Costagliola, J. Orgiazzi, and J. E. Dumont, “Kinetics of thyrotropin-stimulating hormone (TSH) and thyroid-stimulating antibody binding and action on the TSH receptor in intact TSH receptor-expressing CHO cells,” J Clin Endocrinol Metab, vol. 88, no. 11, pp. 5366–5374, Nov. 2003.
[45] A.-C. Gérard, C. Daumerie, C. Mestdagh, S. Gohy, C. De Burbure, S. Costagliola, F. Miot, M.-C. Nollevaux, J.-F. Denef, J. Rahier, B. Franc, J. J. M. De Vijlder, I. M. Colin, and M.-C. Many, “Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas,” J Clin Endocrinol Metab, vol. 88, no. 10, pp. 4977–4983, Oct. 2003.
[46] G. Smits, O. Olatunbosun, A. Delbaere, R. Pierson, G. Vassart, and S. Costagliola, “Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor.,” N Engl J Med, vol. 349, no. 8, pp. 760–766, Aug. 2003.
[47] G. Smits, M. Campillo, C. Govaerts, V. Janssens, C. Richter, G. Vassart, L. Pardo, and S. Costagliola, “Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity.,” EMBO J, vol. 22, no. 11, pp. 2692–2703, Jun. 2003.
[48] C. Vilain, F. Libert, D. Venet, S. Costagliola, and G. Vassart, “Small amplified RNA-SAGE: an alternative approach to study transcriptome from limiting amount of mRNA.,” Nucleic Acids Res., vol. 31, no. 6, p. e24, Mar. 2003.
[49] P. Rodien, S.-C. Ho, V. Vlaeminck, G. Vassart, and S. Costagliola, “Activating mutations of TSH receptor,” Ann Endocrinol (Paris), vol. 64, no. 1, pp. 12–16, Feb. 2003.
[50] V. Panneels, U. Schüssler, S. Costagliola, and I. Sinning, “Choline head groups stabilize the matrix loop regions of the ATP/ADP carrier ScAAC2.,” Biochem Biophys Res Commun, vol. 300, no. 1, pp. 65–74, Jan. 2003.
[51] J. Van Sande, C. Massart, R. Beauwens, A. Schoutens, S. Costagliola, J. E. Dumont, and J. Wolff, “Anion selectivity by the sodium iodide symporter,” Endocrinology, vol. 144, no. 1, pp. 247–252, 2003.
[52] S. Costagliola, J. D. F. Franssen, M. Bonomi, E. Urizar, M. Willnich, A. Bergmann, and G. Vassart, “Generation of a mouse monoclonal TSH receptor antibody with stimulating activity,” Biochem Biophys Res Commun, vol. 299, no. 5, pp. 891–896, Dec. 2002.
[53] S. Costagliola and G. Vassart, “Monoclonal antibodies with thyroid stimulating activity, at last.,” Thyroid, vol. 12, no. 12, pp. 1039–1041, Dec. 2002.
[54] L. Alberti, M. C. Proverbio, S. Costagliola, R. Romoli, B. Boldrighini, M. C. Vigone, G. Weber, G. Chiumello, P. Beck-Peccoz, and L. Persani, “Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism.,” J Clin Endocrinol Metab, vol. 87, no. 6, pp. 2549–2555, Jun. 2002.
[55] S. Claeysen, C. Govaerts, A. Lefort, J. Van Sande, S. Costagliola, L. Pardo, and G. Vassart, “A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist.,” FEBS Lett, vol. 517, no. 1, pp. 195–200, Apr. 2002.
[56] V. Vlaeminck-Guillem, S.-C. Ho, P. Rodien, G. Vassart, and S. Costagliola, “Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist.,” Molecular Endocrinology, vol. 16, no. 4, pp. 736–746, Apr. 2002.
[57] G. Smits, C. Govaerts, I. Nubourgh, L. Pardo, G. Vassart, and S. Costagliola, “Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG.,” Molecular Endocrinology, vol. 16, no. 4, pp. 722–735, Apr. 2002.
[58] A.-C. Gérard, M.-C. Many, C. Daumerie, S. Costagliola, F. Miot, J. J. M. DeVijlder, I. M. Colin, and J.-F. Denef, “Structural changes in the angiofollicular units between active and hypofunctioning follicles align with differences in the epithelial expression of newly discovered proteins involved in iodine transport and organification,” J Clin Endocrinol Metab, vol. 87, no. 3, pp. 1291–1299, Mar. 2002.
[59] S. Costagliola, V. Panneels, M. Bonomi, J. Koch, M. C. Many, G. Smits, and G. Vassart, “Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors,” EMBO J, vol. 21, no. 4, pp. 504–513, Feb. 2002.
[60] C. Daumerie, M. Ludgate, S. Costagliola, and M. C. Many, “Evidence for thyrotropin receptor immunoreactivity in pretibial connective tissue from patients with thyroid-associated dermopathy,” Eur J Endocrinol, vol. 146, no. 1, pp. 35–38, 2002.
[61] L. Alberti, M. C. Proverbio, S. Costagliola, G. Weber, P. Beck-Peccoz, G. Chiumello, and L. Persani, “A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism,” Eur J Endocrinol, vol. 145, no. 3, pp. 249–254, Sep. 2001.
[62] S. Cornelis, S. Uttenweiler-Joseph, V. Panneels, G. Vassart, and S. Costagliola, “Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor,” Biochemistry, vol. 40, no. 33, pp. 9860–9869, Aug. 2001.
[63] S. C. Ho, J. Van Sande, A. Lefort, G. Vassart, and S. Costagliola, “Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity,” Endocrinology, vol. 142, no. 7, pp. 2760–2767, Jul. 2001.
[64] C. Govaerts, A. Lefort, S. Costagliola, S. J. Wodak, J. A. Ballesteros, J. Van Sande, L. Pardo, and G. Vassart, “A conserved Asn in transmembrane helix 7 is an on/off switch in the activation of the thyrotropin receptor,” J Biol Chem, vol. 276, no. 25, pp. 22991–22999, Jun. 2001.
[65] S. Siffroi-Fernandez, S. Costagliola, S. Paumel, A. Giraud, J. P. Banga, and J. L. Franc, “Role of complex asparagine-linked oligosaccharides in the expression of a functional thyrotropin receptor,” Biochem J, vol. 354, no. 2, pp. 331–336, Mar. 2001.
[66] C. Vilain, C. Rydlewski, L. Duprez, C. Heinrichs, M. Abramowicz, P. Malvaux, B. Renneboog, J. Parma, S. Costagliola, and G. Vassart, “Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8,” J Clin Endocrinol Metab, vol. 86, no. 1, pp. 234–238, 2001.
[67] H. S. Chin, D. K. Chin, N. G. Morgenthaler, G. Vassart, and S. Costagliola, “Rarity of anti- Na+/I- symporter (NIS) antibody with iodide uptake inhibiting activity in autoimmune thyroid diseases (AITD),” J Clin Endocrinol Metab, vol. 85, no. 10, pp. 3937–3940, Oct. 2000.
[68] X. De Deken, D. Wang, M. C. Many, S. Costagliola, F. Libert, G. Vassart, J. E. Dumont, and F. Miot, “Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family,” J Biol Chem, vol. 275, no. 30, pp. 23227–23233, Jul. 2000.
[69] J. Pohlenz, L. Duprez, R. E. Weiss, G. Vassart, S. Refetoff, and S. Costagliola, “Failure of membrane targeting causes the functional defect of two mutant sodium iodide symporters,” J Clin Endocrinol Metab, vol. 85, no. 7, pp. 2366–2369, Jul. 2000.
[70] S. Costagliola and G. Vassart, “Comparison of human and porcine TSH receptors,” Thyroid, vol. 10, no. 5, pp. 446–447, May 2000.
[71] S. Costagliola, M. C. Many, J. F. Denef, J. Pohlenz, S. Refetoff, and G. Vassart, “Genetic immunization of outbred mice with thyrotropin receptor cDNA provides a model of Graves’ disease,” J Clin Invest, vol. 105, no. 6, pp. 803–811, Mar. 2000.
[72] S. Costagliola, T. Sunthorntepvarakul, I. Migeotte, J. Van Sande, A. M. Kajava, S. Refetoff, and G. Vassart, “Structure-function relationships of two loss-of-function mutations of the thyrotropin receptor gene,” Thyroid, vol. 9, no. 10, pp. 995–1000, Oct. 1999.
[73] M. C. Many, S. Costagliola, M. Detrait, F. Denef, G. Vassart, and M. C. Ludgate, “Development of an animal model of autoimmune thyroid eye disease,” J Immunol, vol. 162, no. 8, pp. 4966–4974, Apr. 1999.
[74] S. Costagliola, N. G. Morgenthaler, R. Hoermann, K. Badenhoop, J. Struck, D. Freitag, S. Poertl, W. Weglöhner, J. M. Hollidt, B. Quadbeck, J. E. Dumont, P. M. Schumm-Draeger, A. Bergmann, K. Mann, G. Vassart, and K. H. Usadel, “Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease,” J Clin Endocrinol Metab, vol. 84, no. 1, pp. 90–97, 1999.
[75] N. Uyttersprot, S. Costagliola, J. E. Dumont, and F. Miot, “Requirement for cAMP-response element (CRE) binding protein/CRE modulator transcription factors in thyrotropin-induced proliferation of dog thyroid cells in primary culture,” Eur J Biochem, vol. 259, no. 1, pp. 370–378, 1999.
[76] P. Rodien, C. Brémont, M. L. Sanson, J. Parma, J. Van Sande, S. Costagliola, J. P. Luton, G. Vassart, and L. Duprez, “Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin,” N Engl J Med, vol. 339, no. 25, pp. 1823–1826, Dec. 1998.
[77] P. Rodien, F. Cetani, S. Costagliola, M. Tonacchera, L. Duprez, T. Minegishi, C. Govaerts, and G. Vassart, “Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors,” J Clin Endocrinol Metab, vol. 83, no. 12, pp. 4431–4434, Dec. 1998.
[78] S. Costagliola, D. Khoo, and G. Vassart, “Production of bioactive amino-terminal domain of the thyrotropin receptor via insertion in the plasma membrane by a glycosylphosphatidylinositol anchor,” FEBS Lett, vol. 436, no. 3, pp. 427–433, Oct. 1998.
[79] N. Uyttersprot, S. Costagliola, and F. Miot, “A new tool for efficient transfection of dog and human thyrocytes in primary culture,” Mol Cell Endocrinol, vol. 142, no. 1, pp. 35–39, Jul. 1998.
[80] M. Ludgate, M. Crisp, C. Lane, S. Costagliola, G. Vassart, A. Weetman, C. Daunerie, and M. C. Many, “The thyrotropin receptor in thyroid eye disease,” Thyroid, vol. 8, no. 5, pp. 411–413, May 1998.
[81] F. Depoortere, A. Van Keymeulen, J. Lukas, S. Costagliola, J. Bartkova, J. E. Dumont, J. Bartek, P. P. Roger, and S. Dremier, “A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes,” J Cell Biol, vol. 140, no. 6, pp. 1427–1439, Mar. 1998.
[82] S. Costagliola, P. Rodien, M. C. Many, M. Ludgate, and G. Vassart, “Genetic immunization against the human thyrotropin receptor causes thyroiditis and allows production of monoclonal antibodies recognizing the native receptor,” J Immunol, vol. 160, no. 3, pp. 1458–1465, Feb. 1998.
[83] J. Parma, L. Duprez, J. Van Sande, J. Hermans, P. Rocmans, G. Van Vliet, S. Costagliola, P. Rodien, J. E. Dumont, and G. Vassart, “Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas,” J Clin Endocrinol Metab, vol. 82, no. 8, pp. 2695–2701, Aug. 1997.
[84] L. Duprez, J. Parma, S. Costagliola, J. Hermans, J. Van Sande, J. E. Dumont, and G. Vassart, “Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain,” FEBS Lett, vol. 409, no. 3, pp. 469–474, Jun. 1997.
[85] S. Costagliola, M. C. Many, M. Stalmans-Falys, G. Vassart, and M. Ludgate, “Transfer of thyroiditis, with syngeneic spleen cells sensitized with the human thyrotropin receptor, to naive BALB/c and NOD mice,” Endocrinology, vol. 137, no. 11, pp. 4637–4643, Nov. 1996.
[86] L. Alcalde, M. Tonacchera, S. Costagliola, D. Jaraquemada, R. Pujol-Borrell, and M. Ludgate, “Cloning of candidate autoantigen carboxypeptidase H from a human islet library: sequence identity with human brain CPH,” vol. 9, no. 4, pp. 525–528, Aug. 1996.
[87] M. Tonacchera, J. Van Sande, J. Parma, L. Duprez, F. Cetani, S. Costagliola, J. E. Dumont, and G. Vassart, “TSH receptor and disease,” Clin Endocrinol (Oxf), vol. 44, no. 6, pp. 621–633, Jun. 1996.
[88] M. Tonacchera, F. Cetani, S. Costagliola, J. Van Sande, S. Refetoff, and G. Vassart, “Functional characteristics of a variant thyrotropin receptor,” Eur J Biochem, vol. 238, no. 2, pp. 490–494, Jun. 1996.
[89] J. Van Sande, C. Massart, S. Costagliola, A. Allgeier, F. Cetani, G. Vassart, and J. E. Dumont, “Specific activation of the thyrotropin receptor by trypsin,” Mol Cell Endocrinol, vol. 119, no. 2, pp. 161–168, May 1996.
[90] P. Niccoli, S. Costagliola, M. C. Patricot, B. Mallet, M. Benahmed, and P. Carayon, “European collaborative study of LH assay: 3. relationship of immunological reactivity, biological activity and charge of human luteinizing hormone,” J Endocrinol Invest, vol. 19, no. 5, pp. 260–267, May 1996.
[91] C. Le Pommelet, A. Denizot, S. Costagliola, M. Ludgate, E. Nussbaum, G. Kaphan, and C. Oliver, “[Basedow disease following metastatic thyroid cancer],” Presse Med, vol. 25, no. 14, pp. 671–673, Apr. 1996.
[92] M. Catálfamo, C. Roura-Mir, M. Sospedra, P. Aparicio, S. Costagliola, M. Ludgate, R. Pujol-Borrell, and D. Jaraquemada, “Self-reactive cytotoxic gamma delta T lymphocytes in Graves’ disease specifically recognize thyroid epithelial cells,” J Immunol, vol. 156, no. 2, pp. 804–811, Jan. 1996.
[93] M. Tonacchera, S. Costagliola, F. Cetani, J. Ducobu, P. Stordeur, G. Vassart, and M. Ludgate, “Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy; demonstration of direct binding of autoantibodies to the thyrotropin receptor,” Eur J Endocrinol, vol. 134, no. 1, pp. 97–103, 1996.
[94] S. Costagliola, M. C. Many, M. Stalmans-Falys, G. Vassart, and M. Ludgate, “The autoimmune response induced by immunising female mice with recombinant human thyrotropin receptor varies with the genetic background,” Mol Cell Endocrinol, vol. 115, no. 2, pp. 199–206, Dec. 1995.
[95] F. Cetani, S. Costagliola, M. Tonacchera, V. Panneels, G. Vassart, and M. Ludgate, “The thyroperoxidase doublet is not produced by alternative splicing,” Mol Cell Endocrinol, vol. 115, no. 2, pp. 125–132, Dec. 1995.
[96] E. Raspé, S. Costagliola, J. Ruf, S. Mariotti, J. E. Dumont, and M. Ludgate, “Identification of the thyroid Na+/I- cotransporter as a potential autoantigen in thyroid autoimmune disease,” Eur J Endocrinol, vol. 132, no. 4, pp. 399–405, Apr. 1995.
[97] M. Tonacchera, F. Cetani, S. Costagliola, L. Alcalde, R. Uibo, G. Vassart, and M. Ludgate, “Mapping thyroid peroxidase epitopes using recombinant protein fragments,” Eur J Endocrinol, vol. 132, no. 1, pp. 53–61, 1995.
[98] E. Pötter, R. Horn, G. F. Scheumann, H. Dralle, S. Costagliola, M. Ludgate, G. Vassart, J. E. Dumont, and G. Brabant, “Western blot analysis of thyrotropin receptor expression in human thyroid tumours and correlation with TSH-binding,” Biochem Biophys Res Commun, vol. 205, no. 1, pp. 361–367, Nov. 1994.
[99] S. Costagliola, “Recombinant thyrotropin receptor and the induction of autoimmune thyroid disease in BALB/c mice: a new animal model,” Endocrinology, vol. 135, no. 5, pp. 2150–2159, Nov. 1994.
[100] S. Costagliola, L. Alcalde, J. Ruf, G. Vassart, and M. Ludgate, “Overexpression of the extracellular domain of the thyrotrophin receptor in bacteria; production of thyrotrophin-binding inhibiting immunoglobulins,” J Mol Endocrinol, vol. 13, no. 1, pp. 11–21, Aug. 1994.
[101] S. Costagliola, P. Niccoli, M. Florentino, and P. Carayon, “European collaborative study of luteinizing hormone assay: 1. Epitope specificity of luteinizing hormone monoclonal antibodies and surface mapping of pituitary and urinary luteinizing hormone,” J Endocrinol Invest, vol. 17, no. 6, pp. 397–406, Jun. 1994.
[102] S. Costagliola, P. Niccoli, M. Florentino, and P. Carayon, “European collaborative study on luteinizing hormone assay: 2. Discrepancy among assay kits is related to variation both in standard curve calibration and epitope specificity of kit monoclonal antibodies,” J Endocrinol Invest, vol. 17, no. 6, pp. 407–416, Jun. 1994.
[103] S. Costagliola, P. Niccoli, and P. Carayon, “Glycoprotein hormone isomorphism and assay discrepancy: the paradigm of luteinizing hormone (LH),” J Endocrinol Invest, vol. 17, no. 4, pp. 291–299, Apr. 1994.
[104] S. Costagliola, L. Alcalde, M. Tonacchera, J. Ruf, G. Vassart, and M. Ludgate, “Induction of thyrotropin receptor (TSH-R) autoantibodies and thyroiditis in mice immunised with the recombinant TSH-R,” Biochem Biophys Res Commun, vol. 199, no. 2, pp. 1027–1034, Mar. 1994.
[105] S. Costagliola, “Binding assay for thyrotropin receptor autoantibodies using the recombinant receptor protein,” J Clin Endocrinol Metab, vol. 75, no. 6, pp. 1540–1544, Dec. 1992.
[106] M. Ludgate, S. Costagliola, D. Danguy, J. Perret, and G. Vassart, “Recombinant TSH-Receptor for Determination of TSH-Receptor-Antibodies,” Exp Clin Endocrinol Diabetes, vol. 100, no. 4, pp. 73–74, Jul. 1992.
[107] G. Vassart, G. Brabant, S. Costagliola, D. Danguy, C. Gérard, F. Libert, M. Ludgate, C. Maenhaut, M. Parmentier, and R. Paschke, “Molecular genetics of the thyrotropin receptor,” Exp Clin Endocrinol, vol. 100, no. 1, pp. 9–11, 1992.
[108] S. Costagliola, J. Ruf, M. J. Durand-Gorde, and P. Carayon, “Monoclonal antiidiotypic antibodies interact with the 93 kilodalton thyrotropin receptor and exhibit heterogeneous biological activities,” Endocrinology, vol. 128, no. 3, pp. 1555–1562, Mar. 1991.
[109] S. Costagliola, A. M. Madec, M. M. Benkirane, J. Orgiazzi, and P. Carayon, “Monoclonal Antibody Approach to the Relationship between Immunological Structure and Biological Activity of Thyrotropin,” Molecular Endocrinology, vol. 2, no. 7, pp. 613–618, Jul. 1988.
[110] M. M. Benkirane, D. Bon, S. Costagliola, F. Paolucci, B. Darbouret, P. Princé, and P. Carayon, “Monoclonal antibody mapping of the antigenic surface of human thyrotropin and its subunits,” Endocrinology, vol. 121, no. 3, pp. 1171–1177, Sep. 1987.
[111] P. Carayon, E. Martino, L. Bartalena, L. Grasso, C. Mammoli, and S. Costagliola, “Clinical usefulness and limitations of serum thyrotropin measurement by ‘ultrasensitive’ methods. Comparisons of five kits,” Horm Res, vol. 26, no. 1, pp. 105–117, 1987.