Isabelle LIHRMANN-BISSON PhD Cell Biology

Course and current status

CURRENT POSITION : Researcher at the INSERM Institute since 1989, Team 'Functional Genomics and Neuronal and Neuroendocrinre Physiopathology (Head Youssef Anouar) at INSERM U1239, Rouen Normandy University, IRIB Haute-Normandie, France

PREVIOUS POSITIONS: The main steps of I. Lihrmann carees reflect her expertise in Neuroendocrinology, Neuropeptide Communication, and Cellular and Molecular Biology : PhD in 1986 in Hubert Vaudry’s laboratory on the rôle of calcium in adrenocortical cell signaling pathways (Laboratory of Molecular Endocrinology, CNRS URA 650, Rouen, France), 1st postdoctoral fellow  (1986-88) in Jacques Drouin's laboratory on the molecular mechanisms involved in neuropeptide gene transcriptional control (Laboratory of Molecular Genetics of Eukaryotes, Montréal, Canada), 2nd postdoctoral fellow (1988-1989) in Gerard Martens laboratory on neuropeptide gene caracterisation using a comparative approach (Raboud Uni. Dept Animal Physiol, Nijmegen, Holland), academic position at INSERM (1989-) in Neuroendocrinology, on a project aimed at identifiying new neuropeptides using Comparative Genomics and Molecular Biology, leading to the first characterization of the urotensin II gene in mammals, and the revision of our current view of the evolution of the urotensin II/somatostatin gene family.

TEATCHING : Masters 1 and 2 “Biologie-Santé”, Neurosciences

PhD SUPERVISION - 8 PhD, past and present

EVALUATION : Member of the Expert Committee (66-69th sections) of the University of Rouen, (2009-2012) ; Member of the Expert Committee 64th section of the University Paris V (2009) ; Member of the Expert Committee 66-69th section) of MNHN (2014) ; Member of Inserm Scientific Committee N°6 (CSS 6), Neuroscience, Cognition, Mental Health (2012-2016) ; Expert for AERES 2012-204 ; Member of French Society of Neuroendocrinology, French Neuroscience Society ; Member of the Management Committee of the Unit 1239 Inserm ; Reviewer for Brit J Pharmacol; Neurosci, Europ J Nutrition ; Editorial member of Métabolisme, Hormones, Diabètes, Nutrition (MHDN) since 2003.

Scientific summary

 

Our main objective is to characterize new pathways involved in the processes of neurodevelopment and neuroprotection in order to propose new therapeutic targets. We have found previously that the neuropeptide PACAP exerts its powerful neuroprotective effects via the overexpression of a specific thiorodexin-like protein called selenoprotein T (SelT/SELENOT), a potent ROS scavenger. We currently characterize this new antioxidant system using Molecular Biology in combination with Biochemistry .

SELENOT belongs to the family of selenoproteins, unique proteins which most serve oxidoreductase functions, characterized by the presence at least one selenocysteine (Sec), a selenium-containing amino acid. SELENOT expression is very high during development, but intriguingly,  it almost disappears in most adult organs, except in endocrine tissues. Expression of the selenot gene is essential as its absence leads to embryonic lethaly. In addition, mice with conditional SELENOT invalidation have a number of morphological abnormalities, for instance a transient reduction of several brain structures associated with a loss of immature neuron for SELENOT NesKO mice, or a reduction in pancreatic islet size associated with a deficient insulin production and secretion for SELENOT InsKO mice.  Using a yeast two-hybrid screen for membrane protein interactions, SELENOT was found to interact with KCP2], a member of the STT3A-type OST complex which catalyses co-translational N-glycosylation. In vitro, the knockdown (KD) of selenot gene expression leads to an accumulation of misfolded proteins, unfolded protein response (UPR) activation, ER stress, leak of ER Ca2+, ROS production and a decrease in the production and secretion of glycohormones. All these features are consistent with a critical role of SELENOT in the N-glycosylation processing. Biochemical and molecular and cellular approaches are now conducted in order to go a step further and understand the role of SELENOT in N-glycosylation and cell secretion. This research project is supported a number grants (SEINARI, Région Haute Normandie, TransChannel Neurosciences Network).

 

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