CV Science

PHILIPPE LEFEBVRE Research Director at INSERM-PhD in Biochemistry

Course and current status

A-Positions and Honors.   

Research Fellow, Structural Biochemistry Laboratory (Pr M. Dautrevaux) 1984-1988

Postdoctoral fellow at N.I.H., N.C.I., Homone Action and Oncogenesis Section (Dr. G.L. Hager) 1988-1991

Chargé de Recherches 2nde classe INSERM, Biochemistry Department (Pr M. Dautrevaux) 1991-1993

Chargé de Recherches 2nde classe INSERM, Cellular Biology Laboratory (Pr P. Formstecher) 1993-1995

Chargé de Recherches 1st classe INSERM, Cellular Biology Laboratory (Pr P. Formstecher) 1995-1997

Chargé de Recherches 1st classe INSERM, INSERM Unit 459 (Pr P. Formstecher) 1997-2000

Directeur de Recherches 2^nd classe INSERM, INSERM Unit 459 (Pr P. Formstecher) 2000-2006

Directeur de Recherches 2^nd classe INSERM, INSERM Unit 545, Atherosclerosis Department (Pr B. Staels) 2007-2010

Present functions :

Group Leader, Directeur de Recherches 2^nd classe INSERM, INSERM UMR 1011-Univ. Lille 2-Institut Pasteur de Lille (Pr B. Staels)

Group leader

Member of learned societies:

European Association for the Study of Diabetes (EASD); Société Française de Diabétologie (SFD, formerly ALFEDIAM); Member of the Editorial Advisory Board of the Biochemical Journal; Member of the Editorial Board of Journal of Diabetes & Metabolism

Awards:

Award from the Neuman Foundation (Hoechst-Behring) 1984; Fogarty Fellowship, 1988-1991; Labellisation by the “Ligue Nationale contre le Cancer” (2001-2004)

More than 15 research Grants 

B- Selected peer-reviewed publications (5 selected from 60 total).

1-     Lefebvre, B., Benomar, Y., Guédin, A., Langlois, A., Hennuyer, N., Dumont, J., Bouchaert, E., Dacquet, C., Pénicaud, L., Casteilla, L., Pattou, F., Ktorza, A., Staels, B., and Lefebvre, P.The proteasomal degradation of retinoid X receptor gamma reprograms peroxisome proliferator-activated receptor gamma transcriptional activity in obesity. J. Clin. Invest., 2010, (accepted January 27^th, 2010), 120(5): 1454–1468..

2-     Lefebvre P., Cariou B., Lien F., Kuipers F., Staels B.: Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev 2009;89:147-191. 

3-     Carmona, M.C., Louche, K., Lefebvre, B., Pilon, A., Hennuyer, N., Audinot-Bouchez, V., Fievet, C.,  Torpier, G., Formstecher, P., Renard, P., Lefebvre, P., Dacquet, C.,Staels, B. Casteilla, L.and Pénicaud, L. S 26948, a new specific PPARgamma modulator (SPPARM) with potent antidiabetic and antiatherogenic effects.  Diabetes, 2007, (e-published August 17, 2007), 56:2797-2808.

4-     Flajollet S, Lefebvre B, Rachez C and Lefebvre P., Distinct roles of the Steroid Receptor Coactivator 1 and of MED1 in retinoid-Induced transcription and cellular differentiation  J Biol Chem. 2006, (epublished May 24, 2006). 281: 20338-20348

5-     Martin, P.J., Lardeux V. and Lefebvre, P.  The proliferating cell nuclear antigen regulates retinoic acid receptor transcriptional activity through direct protein-protein interaction.  Nuc.Acids.Res., 2005, (e-published July 29, 2005) 33:4311-4321

Scientific summary

Metabolic processes are tightly regulated by a variety of environmental, nervous and endocrine signals whose dysregulations lead to severe pathologies such as diabetes and cardiovascular diseases.  Nuclear receptors (NRs) constitute a class of transcription factors largely involved in metabolic regulations whose activities are, directly or indirectly through heterodimeric partners, modulated by small lipophilic molecules.  Controlling NRs transcriptional cell-specific activities has proven to be a highly valuable therapeutic strategy in several therapeutical fields, including metabolic diseases.  A better understanding of NRs mechanisms of action would undoubtedly improve our ability to manipulate their activities through synthetic ligands and to circumvent side effects observed with NR ligands currently used in therapeutics, as well as identifying novel therapeutic targets.  Indeed, NRs exert their activities through a sequential process relying on surface recognition between multiple cofactors, which is initiated upon ligand docking into the receptor, then followed by chromatin structure alteration and general transcription factor recruitment to the promoter of regulated target genes.  These molecular events have been extensively detailed for a few in vitro model systems and constitute nowadays a paradigm. However, there are significant deviations from this universal scheme, and critical steps and components of the activation process are still unknown for many NRs.  Our research project can therefore be divided in two general themes: (i) Can we reach a level of mechanistic knowledge allowing for the definition of reliable structure-activity relationships for natural and synthetic NR ligands?  (ii) Can we identify and characterize novel components of the NR signaling pathway involved in the pathophysiological progression of cardiovascular and metabolic diseases?  These investigationswill therefore on the one hand unravel novel regulation pathways, and on the other hand, use molecular data to validate and exploit NRs as drugable targets.