Ingrid Langer

Our research

Structure and function of VPAC receptors in physiological and pathological conditions

Our research topics focus on the study of GPCRs and particularly the Vasoactive Intestinal Peptide (VIP) receptors. VPAC1 and VPAC2, two members of the family B of GPCRs, are widely distributed throughout the body and play important role in human physiology such as in development, growth, immune responses, circadian rhythms, neuronal and endocrine control, neuroprotective actions, and in the functions of the digestive, respiratory, reproductive, and cardiovascular systems.

Our particular interest is to study structure, function and molecular mechanisms involved in ligand binding and activation of receptors for the VIP family of peptides using multi-disciplinary approaches combining mutagenesis, pharmacology, molecular biology, biochemistry, protein production and engineering. Our studies led to the identification of residues involved in ligand high affinity binding, receptor activation, G protein coupling as well as receptor phosphorylation and downregulation.

More recently thanks to a collaboration with Jan Steyaert from the Structural Biology Laboratory of the VUB, we generated, by combining genetic immunization, phage display and biopanning, recombinant single chain monoclonal antibodies from Camelid (Nanobodies) targeting several human GPCRs studied in the laboratory. Characterization of these nanobodies revealed that they were new innovative and versatile tools to further investigate the role of these receptors in physiological and pathological conditions.

Overall, we aim to understand how VPAC receptors work at the molecular level with the ultimate goal of potentially developing new diagnostics and therapeutics.

Group members

Ingrid Langer, PharmD, PhD, PI (ilanger@ulb.ac.be)

phone +32 2 555 4129

Jérome Jeandriens, PhD Student
Yosser Bejaoui, Master Thesis Student

Publications

Selected Publications

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

Estienne A, Mellouk N, Bongrani A, Plotton I, Langer I, Ramé C, Petit C, Guérif F, Froment P, Dupont J. Involvement of chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells. Reproduction. 2021 Oct 28;162(6):427-436. doi: 10.1530/REP-21-0265.

Chraibi S, Rosière R, De Prez E, Gérard P, Antoine MH, Langer I, Nortier J, Remmelink M, Amighi K, Wauthoz N.  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.Biomed Pharmacother. 2021 Jul;139:111716. doi: 10.1016/j.biopha.2021.111716. Epub 2021 May 16.

Chraibi S, Rosière R, De Prez E, Antoine MH, Remmelink M, Langer I, Nortier J, Amighi K, Wauthoz N. Pulmonary and renal tolerance of cisplatin-based regimens combining intravenous and endotracheal routes for lung cancer treatment in mice. Int J Pharm. 2021 Apr 15;599:120425. doi: 10.1016/j.ijpharm.2021.120425. Epub 2021 Feb 27.

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

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

I. Langer. Conformational switches in the VPAC1 receptor. Br J Pharmacol 2012, 166(1):79-84.
I. Langer. Mechanisms involved in VPAC receptors activation and regulation: lessons from pharmacological and mutagenesis studies. Front. Endocrinol 2012, 3:129.

A.O. Chugunov, J. Simms, D.R. Poyner, Y. Dehouck, M. Rooman, D. Gilis D and I. Langer. Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation. Mol Pharmacol 2010, 78(3):394-401.

I. Langer, N. Gaspard and P. Robberecht. Pharmacological properties of Chinese hamster ovary cells coexpressing two vasoactive intestinal peptide receptors (hVPAC1 and hVPAC2). Br J Pharmacol 2006; 148(8): 1051-1059.

I. Nachtergael, N. Gaspard, C. Langlet, P. Robberecht and I. Langer. Asn229 in the third helix of VPAC1 receptor is essential for receptor activation but not for receptor phosphorylation and internalization: comparison with Asn216 in VPAC2 receptor. Cell Signal 2006; 18(12): 2121-2130.

I. Langer, C. Langlet and P. Robberecht. Effect of inactivating mutations on phosphorylation and internalization of human VPAC2 receptor. J Mol Endocrinol 2005; 34(2): 405-14.

I. Langer and P. Robberecht. Mutations in the carboxy-terminus of the third intracellular loop of the human recombinant VPAC1 receptor impair VIP stimulated [Ca2+]i increase but not adenylate cyclase stimulation. Cell Signal 2005; 17(1): 17-24.

I. Langer, P. Vertongen, J. Perret, M. Waelbroeck and P. Robberecht. A small sequence in the third intracellular loop of the VPAC1 receptor is responsible for its efficient coupling to the calcium effector. Mol Endo 2002; 16(5): 1089-1096.