GHoPat – GPCRs in homeostasis and pathology

Our research

G protein-coupled receptors (GPCR) represent the largest family among membrane receptors. They play a major role in a variety of physiological and pathophysiological processes and constitute targets for 30% of the active compounds presently used as therapeutic agents.

Our objective is to study new paradigms in activation, signaling and regulation of GPCRs and determine their contribution in pathophysiological processes especially in the gut and the immune system. The experimental approach involves cell and molecular biology, pharmacology, organoid culture technology and in vivo studies.

 

Marie-Isabelle GARCIA Lab

Intestinal stem cell biology

Personnal Web page

 

 

Ingrid LANGER Lab

Structure and function of VIP receptors in physiological and pathological conditions

Personnal Web Page

 

 

 

Jean-Yves SPRINGAEL Lab

Chemokine Receptors in Physiology and Pathology

Personnal Web Page

 

People

 

Principal investigators

 

 

 

Marie-Isabelle Garcia, PhD

PhD in Biochemistry (University Paris 7, FR)

Professor of biochemistry at the Faculty of Medicine (ULB)

 

 

 

 

Ingrid Langer PharmD, PhD

PhD in Pharmaceutical Sciences (ULB, BE)

Professor of pharmacology at the Faculty of Medicine (ULB)

 

 

 

Jean-Yves Springael, PhD

PhD in Chemical Sciences (ULB, BE)

Professor of biochemistry at the Faculty of Medicine (ULB)

 

Lab manager

 

Morgane LEPROVOTS

BA in Cellular biology, genetics, microbiology and physiology (University of Rennes -FR), vocational BA in biology (IUT Tours -FR)

MA degree in life sciences and earth from the EPHE (FR)

 

PhD students

 

 

 

Giulia AGOSTINI

MA in BIiomolecular, genomic and cellular Sciences (University of Parma, IT)

 

 

 

 

 

 

Lilian DEMOLIN, MD

MD Medical sciences (ULB)

 

 

 

 

 

 

Jérôme JEANDRIENS

MA in Biochemistry and Cellular and Molecular Biology (UMons, BE)

 

 

 

 

 

Romane MEERTS

MA in Chemistry and Bio-Industries Bioengineering (ULB, BE)

 

 

 

 

 

Nathalie TUBEZ

MA in Biomedical Sciences, specialized in Translational medicine (ULB, BE)

 

 

 

 

Viktorija VAITKEVIČIŪTĖ

MA Sci. Pharmacology, University College London (UCL, UK)

 

 

 

Master students

 

 

 

Negin Asghariandehkordi

BSc. In Biotechnology (University of Tehran, Iran)

Student in Molecular and Medical Biotechnology at the University of Verona, Italy, and an Erasmus+ student in the MSc in Biomedical Science program at ULB

 

 

 

 

Lilyan Suano

BSc. In Medical Sciences (ULB)

MSc student in Medical sciences at ULB

 

 

Publications

Publications (since 2016)

Duodenal organoids from metabolic dysfunction-associated steatohepatitis patients exhibit absorptive and barrier alterations. Hadefi A, Leprovots M, Dinsart G, Marefati M, Vermeersch M, Monteyne D, Pérez-Morga D, Lefort A, Libert F, Verset L, Liefferinckx C, Moreno C, Devière J, Trépo E, Garcia MI. (2024) Gastro Hep Advances, https://doi.org/10.1016/j.gastha.2024.100599.

The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon. Dinsart G, Leprovots M, Lefort A, Libert F, Quesnel Y, Veithen A, Vassart G, Huysseune S, Parmentier M and Garcia MI (2023) EMBO reports. https://doi.org/10.1038/s44319-023-00013-5

The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking. Degroot, G-N, Lepage, V., Parmentier M. and Springael, J-Y. Cells (2022) (6):1037. doi: 10.3390/cells11061037.

Signal Transduction by VIP and PACAP Receptors. I. Langer, J. Jeandriens, A. Couvineau, S. Sanmukh, D. Latek. Biomedicines (2022) 9;10(2):406. doi: 10.3390/biomedicines10020406.

Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids. A. Hadefi, M. Leprovots, M. Thulliez, O. Bastin, A. Lefort, F. Libert, A. Nonclercq, A. Delchambre, F. Reniers, J. Deviere, MI Garcia. Cell Death Discovery (2022) 8:66 ; https://doi.org/10.1038/s41420-022-00835-7.

Drug Repositioning For Allosteric Modulation of VIP and PACAP Receptors. Langer I, Latek D. Front Endocrinol. (2021) 18;12:711906. doi: 10.3389/fendo.2021.711906.

Involvement of chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells. Estienne A, Mellouk N, Bongrani A, Plotton I, Langer I, Ramé C, Petit C, Guérif F, Froment P, Dupont J. Reproduction. (2021) 162(6):427-436. doi: 10.1530/REP-21-0265.

Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. Proceedings of the National Academy of Sciences. 2021, 118 (25). Vennekens A., Hermans F., Laporte E., Cox B., Modave E., Janiszewski, A., Nys C., Garcia M.I., Pasque V., Kobayashi H., Lambrechts D., Vankelecom H.

Preclinical tolerance evaluation of the addition of a cisplatin-based dry powder for inhalation to the conventional carboplatin-paclitaxel doublet for treatment of non-small cell lung cancer. Chraibi S, Rosière R, De Prez E, Gérard P, Antoine MH, Langer I, Nortier J, Remmelink M, Amighi K, Wauthoz N. Biomed Pharmacother. (2021) 139:111716. doi: 10.1016/j.biopha.2021.111716.

Pulmonary and renal tolerance of cisplatin-based regimens combining intravenous and endotracheal routes for lung cancer treatment in mice. Chraibi S, Rosière R, De Prez E, Antoine MH, Remmelink M, Langer I, Nortier J, Amighi K, Wauthoz N. Int J Pharm. (2021) 599:120425. doi: 10.1016/j.ijpharm.2021.120425.

TAFA4 relieves injury-induced mechanical hypersensitivity through LDL receptors and modulation of spinal A-type K + current. Yoo,S., Santos, C., Reynders, A., Marics, I., Malapert, P., Gaillard, S., Charron, A., Ugolini, S., Rossignol, R., El Khallouqi, A., Springael, JY, Parmentier, M., Saurin, A., Jean-Marc Goaillard, JM, Castets, F., Clerc, N. and Moqrich, A. 2021 Cell Rep doi: 10.1016.

Chemerin added to endothelin-1 promotes rat pulmonary artery smooth muscle cell proliferation adn migration. Hanthazi A, Jespers P, Vegh G, Dubois C, Hubesch G, Springael JY, Dewachter L, Mc Entee K.Front. Physiol. (2020) doi: 10.3389/fphys.2020.00926.

Can BRET-based biosensors be used to characterize G-protein mediated signaling pathways of an insect GPCR, the Schistocerca gregaria CRF-related diuretic hormone receptor ?Lismont E., Verbaket L., Vogel E., Corbisier J., Degroot G., Verdonk R., Verlinder H., Marchal E., Springael J.Y. and Vanden Broeck J. Insect. Biochem. Mol. Biol. (2020) doi: 10.1016/j.ibmb.2020.103392.

LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling. A. Mancini, S. R. Howard, F. Marelli, C. P. Cabrera, M.l R. Barnes, M.l J.E. Sternberg, M. Leprovots, I. Hadji, demetriou, Elena Monti, Al. David, K. Wehkalampi, R. Oleari, A. Lettieri, V. Vezzoli, G. Vassart, A. Cariboni, M. Bonomi, MI Garcia, L. Guasti, and L. Dunkel.JC I Insight. (2020);5(11):e133434.

Lgr5 controls extracellular matrix production by stem cells in the developing intestine. Fernandez-Vallone V., Leprovots M., Gerbier R., Ribatallada-Soriano D., Lefort A., Libert F., Vassart G., Garcia MI. EMBO Rep (2020) vol. 3, no. n/a, p. 038, May 2020.

Coexpression of CCR7 and CXCR4 During B Cell Development Controls CXCR4 Responsiveness and Bone Marrow Homing. Mcheik S, Van Eeckhout N, De Poorter C, Galés C, Parmentier M, Springael JY. Front Immunol. (2019) Dec 18;10:2970. doi: 10.3389/fimmu.2019.02970. eCollection 2019. PMID: 31921208.

Chemerin influences endothelin- and serotonin-induced pulmonary artery vasoconstriction in rats. Hanthazi A., Jespers P., Vegh G., Degroot GN, Springael J.Y., Lybaert P., Dewachter L. and Entee KMC Life Sci. (2019) doi: 10.1016/j.lfs.2019.116580.

A Molecular Dynamics Study of Vasoactive Intestinal Peptide Receptor 1 and the Basis of Its Therapeutic Antagonism. Latek, D., Langer, I., Krzysko, K., & Charzynski, L. International Journal of Molecular Sciences (2019) 20(18), 4348. doi:10.3390/ijms20184348.

Development by Genetic Immunization of Monovalent Antibodies Against Human Vasoactive Intestinal Peptide Receptor 1 (VPAC1), New Innovative, and Versatile Tools to Study VPAC1 Receptor Function. X. Peyrassol, T. Laeremans, V. Lahura, M. Debulpaep, H. El Hassan, J. Steyaert, M. Parmentier, I. Langer. Front Endocrinol (2018), 9:153 doi:10.3389/fendo.2018.00153.

Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis and Cardiac Function After Myocardial Infarction. Horckmans M, Bianchini M, Santovito D, Megens RTA, Springael J.Y., Negri I, Vacca M, Di Eusanio M, Moschetta A, Weber C, Duchene J, Steffens S Circulation (2018) 137: 948-960.

Partial agonist and biased signaling properties of the synthetic enantiomers J113863/UCB35625 at chemokine receptors CCR2 and CCR5. Corbisier, J., Galès, C., Huszagh, A., Parmentier M. and Springael J.Y. J. Biol. Chem. (2017) 292: 575-584.

LGRs receptors as peculiar GPCRs involved in cancer (Review). Garcia MI. J Stem Cell Res Med (2017), doi: 10.15761/JSCRM.1000116.

Ex vivo culture of gastric spheroids. Fernandez Vallone V., Leprovots M., Vassart G and Garcia MI. Bio-protocols. (2017). DOI 10.21769/2089.

Ex vivo culture of adult antral glands. Fernandez Vallone V., Leprovots M., Vassart G and Garcia MI. Bio-protocols. (2017). DOI 10.21769/2088.

Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage: Fernandez Vallone V, Leprovots M, Strollo S, Vasile G, Lefort A, Libert F, Vassart G, Garcia MI.

Development. (2016) May 1;143(9):1452-63. doi: 10.1242/dev.131490. Epub 2016 Mar 17.

Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor. X. Peyrassol, T. Laeremans, M. Gouwy, V. Lahura, M. Debulpaep, J. Van Damme, J. Steyaert, M. Parmentier, I. Langer. J Immunol (2016), 196(6):2893-901.

Signaling properties of chemerin receptors CMKLR1, GPR1 and CCRL2. De henau, O., Degroot, G.N., Imbault, V., Robert, V., De Poorter, C., Mcheik, S., Galés, C., Parmentier, M. and Springael, J.Y. PLoSONE (2016) 11:e0164179.L

LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea. Zak, M.; Van Oort, T.; Hendriksen, F.G; Garcia MI; Vassart, G; Grolman, W. Front Cell Neurosci. (2016); 10: 186. doi: 10.3389/fncel.2016.00186 PMCID: PMC4988241

Stem Cells in Adult Homeostasis, Regeneration and Tissue Development of the Digestive Tract Epithelium. V. Fernandez-Vallone and MI. Garcia. Int J Stem Cell Res Ther (2016), 3:038 Volume 3 | Issue 2 ISSN: 2469-570X

Building and rebuilding gastric epithelium: Trop2 as a common denominator. V. Fernandez-Vallone and MI. Garcia. Atlas of Science, another view on science. Published online August 15th, 2016.

Modular Integrated Secretory System Engineering in Pichia pastoris To Enhance G-Protein Coupled Receptor Expression. Claes, K., Vandewalle, K., Laukens, B., Laeremans, T., Vosters, O., Langer, I., Parmentier, M., Steyaert, J., & Callewaert, N. ACS synthetic biology (2016). doi:10.1021/acssynbio.6b00032

Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy. Rosiere, R., Van Woensel, M., Mathieu, V., Langer, I., Mathivet, T., Vermeersch, M., Amighi, K., & Wauthoz, N. International journal of pharmaceutics (2016). doi:10.1016/j.ijpharm.2016.01.073.

Contact

Email : ghopat@ulb.be

Follow us on X: GHoPaT@GHoPaTgroup

Follow us on bluesky : @ghopat.bsky.social

Marie-Isabelle Garcia, Email : Marie.Garcia@ulb.be

Ingrid Langer, Email : Ingrid.Langer@ulb.be

Jean-Yves Springael, Email : Jean-Yves.Springael@ulb.be