Biography

Séverine Morisset-LOPEZ is a CNRS (The National Center for Scientific Research) researcher at the Center for Molecular Biophysics (CBM) in Orleans, France. She has long-standing expertise in neuropharmacology and GPCRs fields. She developed skills in several areas of research by conducting in vitro molecular and cellular pharmacology experiments (on cell lines and primary cultures of neurons) as well as in vivo experiments (neurochemical, immunohistological and behavioral studies) on animals’ models
Dr Morisset-Lopez obtained her PhD in Molecular Pharmacology from Paris V University (France) in 1999 and joined the Center of Psychiatry and Neurosciences in Paris in 2002. She has contributed substantilly to the molecular study of the histamine H3 receptor and obtained several important results not only for basic researches on the regulation of the receptor but also for the clinical development of its ligands in neurodegenerative diseases (Morisset et al, JPET 1999, Morisset et al, Nature, 2000; Gbahou et al, PNAS 2003). In 2009, she moved to the Center for Molecular Biophysics (CBM) to Orleans. In collaboration with P Marin (IGF, Montpellier), she contributed to characterize the role of interacting proteins in 5-HT6 receptors signalling (Duhr et al, Nat Chem Biol 2014) and demonstrated how the physical interaction between the neurofibromin, the protein involved in neurofibromatosis type I and the serotonin 5-HT6 receptor promotes the constitutive activity of the receptor (Deraredj Nadim, PNAS, 2016).

She is now the co-leader of the group “Cell microenvironment and receptors pharmacology” at CBM where she has recently developed a project on the serotonin 5-HT7 receptor, belonging to the GPCR family. The main objectives are to investigate the molecular mechanisms involved in the activation of 5-HT7 receptor, the dynamics of its interactions with protein partners, its downstream signaling and the role of this receptor in pathologies of the central nervous system. We are also participating in the development and identification of new 5-HT7 ligands in collaboration with Pr Suzenet (ICOA, Orléans, France) and Pr Bojarski (PANS, Krakow, Poland) (Deau et al, J Med Chem, 2015). For this purpose, the team has developed various biophysical resonance energy transfer (RET)-based approaches, including BRET, nanoBRET, FRET, TR-FRET and Alpha Screen assays.

Ongoing studies are also focused on LINGO-1, an attractive therapeutic target for the treatment of neurodegenerative and demyelinating diseases. We have recently demonstrated that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that molecules affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological way to modulate its function and provides a new strategy for drug discovery (Morisset et al, patent 2011 and Cobret et al, Br J Pharmacol, 2015). Our objective is now to investigate the possible dysregulation of LINGO-1 and its homologs in neuropathologies and to identify new modulators of LINGO-1 such as biomolecules and/or chemicals compounds able to modulate its expression/function

Author of 40 journal articles, 8 reviews and 1 patent

Scientific skills and expertises:
Biology of receptors: Cellular and molecular pharmacology, BRET analysis, cell signalling, biochemistry
Neurobiology: primary neuronal culture, tissue section, IHC, neurochemical and behavioural experiments in rodents.