Our research
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
Group members
Sabine Costagliola, PI, FNRS Research Director (scostag@ulb.ac.be)
IRIBHM 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).
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.
ULB researcher :
Mírian Romitti
Mirian.romitti@ulb.be
Mirian Romitti is ULB scientific researcher at IRIBHM. She has done her Ph.D studies in Brazil (PhD (2014) in Biomedical Sciences: Endocrinology from University Federal of Rio Grande do Sul, Brazil) and after that joined the Costagliola Lab as Post-doctoral researcher. This collaboration started with the goal of generating organoid models to study thyroid diseases, such as hypothyroidism and cancer. After two years, due to the advances achieved, she received a “Chargé de recherche” position from FNRS. During this period, she worked on generating a thyroid cancer model using mouse organoids previously generated in the lab. Also, under the framework of the Horizon 2020 program, as part of the SCREENED consortium, she has been working in collaboration with other research groups generating tools to study the toxic effect of Endocrine Disruptors on the thyroid gland. More recently, she successfully demonstrated the generation of a protocol, starting from human embryonic stem cells, which results in thyroid hormones-producing human thyroid organoids. This model comprised a milestone in the field and opens a new window on the morphogenetic processes and gene regulatory networks associated with thyroid development.
In her work performed at IRIBHM, Mirian has contributed to the understanding of the mechanisms regulating the thyroid gland from development to function and how thyroid disorders, such as cancer and hypothyroidism can be tackled using new technologies such as organoids.
Postdoctoral Fellow:
Eduardo Rios
eduardo.andres.rios.morris@ulb.be
Eduardo Rios is a postdoctoral fellow in Costagliola’s lab. He received his bachelor’s and master’s degrees in biochemistry from Andrés Bello University in Chile. He then moved to Brazil to pursue his PhD in ‘ Morphological Sciences: Developmental Biology’ at the Institute of Biomedicine of the Federal University of Rio de Janeiro (UFRJ). During all these years, Eduardo worked with zebrafish as a model to understand the mechanisms by which cell adhesion controls some aspects of gastrulation and cell behaviour during development.
After his PhD, Eduardo went to CRBM/CNRS in Montpellier – France to complete his first postdoc. There he deepened the mechanisms of cell adhesion in cancer aggressiveness using in vivo and in vitro models. He then returned to Brazil, where he obtained a position as visiting professor at the UFRJ Faculty of Medicine. There he worked as a researcher studying the effects of exposure to different endocrine disrupting chemicals on thyroid physiology using different in vivo models.
Eduardo started in Costagliola’s lab in March of 2023 working in thyroid cancer using thyroid organoids models.
PhD Students:
Daniela Aparicio
daniela.aparicio.quinonez@ulb.be
Daniela Aparicio graduated from a bachelor’s degree in Biochemistry and Microbiology from the Universidad del Valle de Guatemala in Guatemala City. After that she moved to Leuven, Belgium and completed a master’s degree in Biochemistry and Biotechnology at the KU Leuven in 2021. Passionate about molecular developmental biology, she studied octopus neurodevelopment for her master thesis. Later, interested in biomedical research with a less confidential experimental model, she joined the Costagliola lab in 2022 as a PhD student. Her project is focused on modeling congenital thyroid diseases with human thyroid organoids.
Meghna Shankar
Parakkal.Meghna.Shankar@ulb.be
Meghna graduated from the University College Dublin, Ireland in 2018. The title of her MSc thesis was “Characterisation of an autosomal recessive blind zebrafish model, with a putative mutation in the gene encoding abca4b (photoreceptor cell–specific ATP-binding cassette transporter)”. She has previously worked in Bangalore, India, in genetic testing and NGS based diagnostic laboratories at the Centre for Human Genetics and Medgenome Labs Private limited as a Research Associate. Meghna has an undergraduate degree Bachelor of engineering in Biotechnology from PES University Bangalore, India. She joined the Costagliola laboratory in 2018 for a PhD to work on a zebrafish model to study thyroid cell specification within the foregut endoderm.
Agathe Kornreich
agathe.kornreich@ulb.be
Agathe graduated as a bioengineer from the University of Liège, Belgium, in 2022. Being very interested in molecular biology and biomedical science, she moved to Toulouse to the Canceropole (CRCT) for her master’s thesis. The title of her master’s thesis was “Interest of co- treatment with chemotherapy and oncolytic viruses in pancreatic cancer”. She joined the Costagliola lab as a graduate student in 2022. Her project focuses on studying the molecular mechanism that modulates TSH biosensitivity in organoid models.”
Alessandra Boggian
alessandra.boggian@ulb.be
Alessandra obtained a bachelor’s in Medical Biotechnology from the University of Ferrara (2019). Subsequently, she graduated in a master’s in Biomedical Sciences from the University of Amsterdam (2021). She conducted her research projects at the Amsterdam University Medical Center (UMC) and the Swammerdam Institute for Life Science (SILS). She became interested in regenerative medicine and developmental biology during her project in cardiac regeneration and engineered tissue production and modeling. She started her PhD project in November 2022 in Costagliola’s lab. In her project, she studies the role of insulin in the development of lung organoids derived from embryonic stem cells.
Laura Chomette
Laura.Chomette@ulb.ac.be
Laura Chomette graduated from medical school at ULB in 2015 and specialized in Cardiology in 2018. She is currently a PhD student at the IRIBHM and Erasme Hospital, supervised by Pr Antoine Bondue and funded by the Fonds Erasme. The title of her PhD is Heritable Pulmonary Arterial Hypertension: molecular insights through genetics and induced pluripotent stem cells.
Publications
Costagliola, S., Singh, S. “Emerging Technologies in Thyroid Biology: Pushing the Frontiers of Thyroid Research”, Molecular and Cellular Endocrinology, https://doi.org/10.1016/j.mce.2023.111912
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Mírian Romitti, Barbara de Faria da Fonseca, Gilles Doumont, Pierre Gillotay, Adrien Tourneur, Sema Elif Eski, Gaetan Van Simaeys, Laura Chomette, Helene Lasolle, Olivier Monestier, Dominika Figini Kasprzyk, Vincent Detours, Sumeet Pal Singh, Serge Goldman, Samuel Refetoff, Sabine Costagliola, “Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism” Nat Commun 13, 7057 (2022). https://doi.org/10.1038/s41467-022-34776-7, https://doi.org/10.1038/s41467-022-34776-7
Fonseca B F, Barbee C, Romitti M, Eski S E, Gillotay P, Monteyne D, Perez-Morga D, Refetoff S, Singh S P and Costagliola S “Foxe1 orchestrates thyroid and lung cell lineage divergence in mouse stem cell-derived organoids”, 2022 bioRxiv 2022.05.16.492074. https://doi.org/doi:10.1101/2022.05.16.492074.
Pierre Gillotay, Mirian Romitti, Benjamin Dassy, Benoit Haerlingen, Meghna Parakkal Shankar, Barbara De Faria Da Fonseca, Panos G. Ziros, Sumeet Pal Singh, Gerasimos Sykiotis, Sabine Costagliola.”Nrf2 promotes thyroid development and hormone synthesis”, bioRxiv 2022.02.27.482168; doi: https://doi.org/10.1101/2022.02.27.482168
Benoit Haerlingen, Robert Opitz, Isabelle Vandernoot, Angelo Molinaro, Meghna Shankar, Pierre Gillotay, Achim Trubiroha, Sabine Costagliola,”Mesodermal FGF and BMP govern the sequential stages of zebrafish thyroid specification” bioRxiv 2020.08.13.249540; doi: https://doi.org/10.1101/2020.08.13.249540
M. Romitti, S. E. Eski, B. F. Fonseca, P. Gillotay, S. P. Singh, and S. Costagliola, “Single-cell trajectory inference guided enhancement of thyroid maturation in vitro using TGF-beta inhibition,” Front Endocrinol 12, 657195 (2021).
A. Sassi, J. Désir, V. Janssens, M. Marangoni, D. Daneels, A. Gheldof, M. Bonduelle, S. Van Dooren, S. Costagliola, and A. Delbaere, “Novel inactivating follicle-stimulating hormone receptor mutations in a patient with premature ovarian insufficiency identified by next-generation sequencing gene panel analysis,” F&S Reports, vol. 1, no. 3, pp. 193–201, Dec. 2020.
P. Gillotay, M. P. Shankar, S. E. Eski, S. Reinhardt, A. Kraenkel, J. Blaesche, A. Petzold, G. Kesavan, C. Lange, M. Brand, V. Detours, S. Costagliola, and S. P. Singh, “Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte diversity in the zebrafish thyroid gland,” EMBO Rep, vol. n/a, no. n/a, p. e50612, Nov. 2020.
Vandernoot I, Haerlingen B, Gillotay P, Trubiroha A, Janssens V, Opitz R, Costagliola S. Enhanced Canonical Wnt Signaling During Early Zebrafish Development Perturbs the Interaction of Cardiac Mesoderm and Pharyngeal Endoderm and Causes Thyroid Specification Defects. Thyroid. 2020 Sep 16. doi: 10.1089/thy.2019.0828.
Moroni, F. Barbaro, F. Caiment, O. Coleman, S. Costagliola, G. Di Conza, L. Elviri, S. Giselbrecht, C. Krause, C. Mota, M. Nazzari, S. R. Pennington, A. Ringwald, M. Sandri, S. Thomas, J. Waddington, and R. Toni, “SCREENED: A Multistage Model of Thyroid Gland Function for Screening Endocrine-Disrupting Chemicals in a Biologically Sex-Specific Manner,” IJMS, vol. 21, no. 10, pp. 3648–23, May 2020.
Duerinckx, S., Jacquemin, V., Drunat S., Vial Y., Passemard S., Perazzolo C., Massart A, Soblet, J., Racapé J., Desmyter L., Badoer C., Papadimitriou S., Le Borgne Y-A., Lefort A., Libert F., De Maertelaer V., Rooman M., Costagliola S., Verloes A., Lenaerts, T., Pirson I. & Abramowicz M. (2019, in printing) Digenic inheritance of human primary microcephaly delineates centrosomal and non centrosomal pathways. Hum Mutat. 2019 Nov 7. doi: 10.1002/humu.23948.
Nicoletta Giusti, Pierre Gillotay, Achim Trubiroha, Robert Opitz, Jacques-Emile Dumont, Sabine Costagliola, Xavier De Deken, “Inhibition of the thyroid hormonogenic H2O2 production by Duox/DuoxA in zebrafish reveals VAS2870 as a new goitrogenic compound”, Molecular and Cellular Endocrinology, 2019, 110635, ISSN 0303-7207, https://doi.org/10.1016/j.mce.2019.110635.
Benoit Haerlingen, Robert Opitz, Isabelle Vandernoot, Achim Trubiroha, Pierre Gillotay, Nicoletta Giusti, Sabine Costagliola. “Small Molecule Screening in Zebrafish Embryos Identifies Signaling Pathways Regulating Early Thyroid Development”. 2019, Sept 11, Thyroid. https://doi.org/10.1101/55186
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
S. Costagliola, “Thyrotropin receptor activation by autoantibodies: A butterfly effect,” Ann Endocrinol (Paris), vol. 72, no. 2, pp. 114–116, Apr. 2011.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
S. Costagliola and G. Vassart, “Monoclonal antibodies with thyroid stimulating activity, at last.,” Thyroid, vol. 12, no. 12, pp. 1039–1041, Dec. 2002.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
S. Costagliola and G. Vassart, “Comparison of human and porcine TSH receptors,” Thyroid, vol. 10, no. 5, pp. 446–447, May 2000.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.