Cell microenvironment and receptor pharmacology

Applications to nervous and cutaneous domains

Website in progress

Our thematic group studies cells in the context of their physiopathological microenvironment to determine relevant and effective biological targets in situ. We study in particular the activity and expression of membrane receptors which are regulated by the cell microenvironment and which also participate to its regulation.

We are interested in the role of microenvironment in the regulation of physiological (aging) and pathological processes (tumor, inflammation, oxidative stress,…). We develop various 2D and 3D cellular models (endothelial cells, nervous system cells, cutaneous cells, tumor cells) respecting the rate of intratissular oxygenation, physioxia or hypoxia. Our goal is to identify biomarkers involved in these processes, such as proteins, metabolites or microRNAs (new regulators of genome expression) and to study the crosstalk between membrane receptors and cellular microenvironment. We are also developing new selective and powerful pharmacological tools targeting these receptors to improve our fundamental knowledge of the molecular bases  of their activation and for therapeutic applications.

Our approach is at the molecular (BRET, qPCR techniques), cellular (primary cells, lineages, 3D organoids reconstruction, cell dynamics) levels but also in vivo in animals (orthotopic tumor models, transgenic mouse models). Our goal is to get closer to in situ conditions to define relevant targets and to use these biomimetic models to validate the effectiveness of the pharmacological tools we develop (chemical molecules, nanobodies, miRs or antagomiRs).

Relevant publications :

  • El Khamlichi C, Reverchon-Assadi F, Hervouet-Coste N, Blot L, Reiter E, Morisset-Lopez S. Bioluminescence Resonance Energy Transfer as a Method to Study Protein-Protein Interactions: Application to G Protein Coupled Receptor Biology, Molecule (2019) Feb 1;24(3).
  • Krzysztof Klimkiewicz, Kazimierz Weglarczyk, Guillaume Collet, Alan Guichard, Alicja Jozkowicz, Jozef Dulak, Tadeusz Sarna, Catherine Grillon, Claudine Kieda, A 3D model of tumor angiogenic microenvironment to monitor hypoxia effects on cell interactions and cancer stem cell selection. Cancer Letters (2017) 396, 10-20.
  • W Deraredj Nadim, S Chaumont-Dubel, F Madouri, L Cobret, M L De Tauzia, H Bénédetti, P Marin and S Morisset-Lopez. Physical Interaction between Neurofibromin and Serotonin 5-HT6 Receptor Promotes Receptor Constitutive Activity. Proc Natl Acad Sci U S A, (2016) 113 (43): 12310-12315.
  • Cobret L, De Tauzia M, Ferent J, Traiffort E, Hénaoui I, Godin F, Hélène Bénédetti and Séverine Morisset-Lopez Targeting the cis-dimerization of LINGO-1 with small-molecule affects its dowstream signaling. Br J Pharmacol, (2015) (172): 841-856.
  • Carreau A, El Hafny-Rahbi B., Matejuk A., Grillon C.,  Kieda C. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med (2011) 15(6): 1239-1253.