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Partner 1a team leader:
The Treuter laboraty investigate the intricate relationship between metabolism and inflammation that emerges as a key feature of the metabolic syndrome and its major components obesity, insulin resistance, and type 2-diabetes. The main objective is to study transcriptional and epigenetic control of metabolism and inflammation in pathophysiology and how post-translational modifications of the oxysterol receptors (LXRs) affect transcriptional regulation of metabolic pathways. The team hopes to contribute to an advanced understanding of metabolic disease mechanisms and to translate this knowledge into new therapeutic strategies.
The Treuter laboratory will direct the phenotypic analysis of mouse models in WP8.4 and investigate how disease conditions alter the post-translational modification status of transcription factors, thereby affecting physiological pathways. A combination of targeted and screening approaches are proposed to identify changes in modification states of major liver transcription factors in mouse models.
Over the last few years the Treuter team has portrayed the important roles of LXRs and their transcriptional networks in controlling metabolic pathways. Significant discoveries include the demonstration that LXRs are modified by post-translational mechanisms that render the receptors available to control alternative pathways in metabolism and inflammation. Moreover, interactions with the coregulator GPS2 trigger LXR-dependent epigenetic changes of regulatory DNA elements that control genes involved in lipid and cholesterol metabolism. Most recent collaborations with clinical researchers have identified alterations in anti-inflammatory receptor-coregulator pathways that are linked to the chronic inflammatory status of liver and adipose tissue during obesity. Professor Treuter is a participant in the Nordic Network of National Centers of Excellence (NORGEN) and has participated in the European CoE (CASCADE). He has served as consultant for the Biotech company KaroBio AB (Sweden).
1. Theofilopoulos et al. (2013) Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nature Chemical Biology Feb;9(2):126-33.
2. Toubal A, et al. (2013) GPS2/SMRT corepressor pathway dysregulation coincides with obesity-linked adipocyte inflammation. Journal of Clinical Investigation Jan 2;123(1):362-79.
3. Vedin LL, et al. (2013) The oxysterol receptors LXRα and LXRβ suppress proliferation in the colon. Molecular Carcinogenesis Nov;52(11):835-44.
4. Jakobsson T, et al. (2012) Liver X receptor biology and pharmacology: new pathways, challenges and opportunities. Trends Pharmacol Sci. Jul;33(7):394-404.
5. Venteclef N, et al. (2010) GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXR beta in the hepatic acute phase response. Genes & Development 24(4):381-95.
6. Jakobsson T, et al. (2009) GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus. Molecular Cell 34(4):510-8.