CNRS is a state-funded science and technology establishment placed under the authority of the French Minister for Research. CNRS research units are located throughout France, and employ a large body of tenured researchers, engineers, and support staff. Laboratories are all on renewable four-year contracts, with bi-annual evaluation.The UMR7221 “Evolution of Endocrine Regulations”, is affiliated with the CNRS and the National Museum of Natural History. Research focuses on nuclear receptors, particularly thyroid hormone receptors and their roles in development and aging.
Partner 2 team leaders:
Professor Barbara Demeneix
Dr Giovanni Levi
B. Demeneix will direct the phenotypic analysis of thyroid hormone signalling integration of metabolic response in the mouse models in WP5 and investigate how transplanted hepatocytes (that are the site of expression of one the main deiodinases D1, that activates the thyroid hormone ‘prohormone’, T4 into the biologically active form T3) will modify circulating thyroid hormone availability and thereby modulate not only peripheral metabolism but also hypothalamic responses governing energy balance and feeding. A genetic susceptibility/mutation transferred through liver-specific iPSC graft could propagate to peripheral tissue through this major endocrine pathway, affecting hypothalamic structures and thereby modulating not only thyroid hormone production in the thyroid that in turn affects lipid metabolism at multiple levels, but also neuronal output, the overall effect being modulation of energy expenditure, feeding behaviour or glucose metabolism. G. Levi will provide expertise in design of new murine models for modulating thyroid hormone responses in the hypothalamus.
Prof Barbara A Demeneix – MNHN Professor – has a noteworthy track-record in basic and translational research (>140 publications in endocrinology and physiology) and in management of international and national research consortia. Besides her role as Head of Department and Research unit, she is co-ordinator of SWITCHBOX, an EU Project addressing the links between homeostasis and aging. Dr G. Levi – CNRS Research director – has a long-lasting experience in the generation and analysis of mice carrying targeted mutations to elucidate the function of transcription factors during development and aging. Recently he has generated conditional and inducible mutant strains focusing in particular on the steroid axis. Dr Marie-Stéphanie Clerget-Froidevaux – Assistant professor: main research focus is thyroid hormone regulation of the TRH gene in the hypothalamus, control of metabolism. Mme Isabelle Seugnet – Research Engineer trained as a biochemist. She has experience in real time qPCR, RNA extraction, ISH and is currently managing the implantation of laser microdissection technique in the lab.
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2. A. Lopez-Juarez, et al. (2012) Thyroid Hormone Signaling Acts as a Neurogenic Switch by Repressing Sox2 in the Adult Neural Stem Cell Niche. Cell Stem Cell, 10 531-43.
3. Bouhali K, (2011) Allelic Reduction of Dlx5 and Dlx6 Results in Early Follicular Depletion: A New Mouse Model of Primary Ovarian Insufficiency. Hum Mol Genet. 20 2642-50.
4. Decherf S, et al. (2010) Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression. Proc Natl Acad Sci U S A.;107(9):4471-6.
5. Froidevaux MS, et al. (2006) The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone in vivo. EMBO Rep (10):1035-9