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Contact
Béatrice Desvergne
Center for Integrative Genomics
Faculty of Biology and Medicine
University of Lausanne
Génopode Building
Dorigny Campus
1015 Lausanne
Switzerland
Phone: +41 (0)21 692 4140
Email : Beatrice.Desvergne@unil.ch
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Béatrice Desvergne was trained as a MD. She initially specialized in Anesthesiology and Resuscitation and practiced medicine for a few years, while continuing her education in more fundamental aspects of human biology. From 1988 to 1992, she carried out a post-doctoral stay at the National Institutes of Health in Bethesda, first as a visiting fellow and then as a visiting associate in the National Institute of Diabetes and Digestive and Kidney. She then decided to continue working in fundamental research and joined the University of Lausanne as an Assistant Professor. She then became Associate Professor and, in 2008, full Professor. She joined the Center for Integrative Genomics in 2003. She is presently Vice-Dean of the Faculty of Biology and Medicine and President of the Section of Fundamental Sciences.
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Current research
Nuclear receptors, which mediate intracellular hormone action, play a crucial multi-faceted role in coordinating growth during development, and homeostasis at adult stage. There are 48 members of the nuclear receptor superfamily, among which the peroxisome-proliferator activated receptors (PPARs) act as fatty acids sensors, responding to dietary as well as to endogenous challenges. Accordingly, they have an integrative role in controlling the expression of genes regulating the storage, mobilization, and/or utilization of lipids. This integrative role goes beyond lipid metabolism and affect as well glucose metabolism, regulating many facets of energy metabolism. These activities operate both at cell levels and at systemic levels, explaining the wide range of PPAR actions, and the major therapeutic interest of synthetic ligands that operate through PPARs.
Using various molecular, cellular, and animal approaches, our studies are aimed at understanding how PPARs are integrated in the main pathways that shape the organism during development on the one hand and maintain systemic homeostasis on the other hand. After generating PPAR mutant mice, our activities have been centered on revealing and understanding at the molecular levels the phenotypic expressions of PPAR mutations. Taking them as leads to explore the physiopathological significance, we also explore novel therapeutic advances that PPARs carry.
Our current work is focused on understanding the nuclear receptor-mediated regulatory events that link cell metabolism and development on the one hand, and response to injury or to chemically-induced endocrine disruption on the other hand. While initially centered on PPAR regulated pathways, our aim is to model the regulatory networks that the nuclear receptors, or a subset of them, are governing and depending on, in metabolically relevant contextes.
Keywords:
Nuclear receptors, PPARs, gene regulatory networks, metabolism, mouse models
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Role within the CycliX Consortium
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We will initially make use of our competences in metabolic regulation and homeostasis linked to nutrition events. Pertaining to the nutrient-response cycle, the liver is the main organ involved in metabolism, performing key roles in carbohydrate, lipid, and protein metabolism, in addition to detoxification and other functions. Most of the nuclear receptors are expressed in the liver and they are likely to be important contributors to the cycles to be explored. After identification, by the consortium, of the active enhancer and silencer elements at the different phases of the nutrition cycle and genome-wide localisation of co-activators and co-repressors, we will identify and assess the most important transcription regulators acting at the mapped cis-regulatory sites. The behavior of these regulators identified in the nutrient response will be further investigated along the cell cycle and the circadian rhythm in the liver, in order to know whether they are or not connecting nodes. Such knowledge will feed the process of modelling the connection between the three cycles. |
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Nadra, K., Anghel, S.I., Joye, E., Tan, N.S., Basu-Modak, S., Trono, D., Wahli, W., and Desvergne, B. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta. Mol Cell Biol. 2006, 26:3266-81.
Desvergne, B., Michalik, L., and Wahli, W. Transcriptional control of metabolism. Physiological Review 2006, 86:465-514.
Anghel, S.I., Bedu, E., Vivier, C.D., Descombes, P., Desvergne, B., and Wahli. W. Adipose tissue integrity as a prerequisite for systemic energy balance: a critical role for peroxisome proliferator-activated receptor gamma. J Biol Chem. 2007 282:29946-57.
Sanderson, L.M., Degenhardt, T., Desvergne, B., Müller, M., and Kersten, S. PPAR / but not PPAR serves as plasma free fatty acid sensor in the liver. Mol Cell Biol. 2009 29 :6257-67
Feige, J.N., Gerber, A., Yang, Q., Bedu, E., Gelman, L., Auwerx, J., Gonzalez, F.J., and Desvergne, B. The pollutant di-ethyl-hexyl-phthalate exerts opposite actions on diet-Induced obesity in mouse and human models via PPAR?-dependent mechanisms . Env Health Perspect, 2009 Oct, in press.
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