Elucidation of the molecular mechanisms taking place during the shift in gene expression in the transition between cell proliferation and cell differentiation will help not only to understand why the cell proliferate instead of differentiate in response to external stimuli, but also will help to design new strategies to modify such process.

A cross-talk between metabolic regulators, such as nuclear receptors, and cell cycle regulatory proteins might exist in order to insure a coordinated response to external stimuli. Disturbances in this cross-talk may result in impaired metabolism, or proliferative disorders.

Our research projects try, on the one hand, to implicate metabolic regulators, such as PPARg in the control of cell proliferation. Forcing proliferating tumoral cells to acquire a differentiated phenotype, through activation of PPARg should be considered as an alternative or complementary therapy for the treatment of cancer.

Moreover, the analysis of the participation of cell cycle regulatory proteins in metabolic processes will open up new perspectives for the treatment of metabolic disorders such as obesity or diabetes. Two distinct, but convergent projects are being developped :

Differentiation therapy for prostate cancer using PPARg agonists in combination with HDAC and EGFR inhibitors. We have observed a synergy of these factors in the control of metabolic processes. We want now to demonstrate that the same synergy is observed in the control of prostate cancer. The molecular mechanisms will be elucidated. Preclinical studies are performed and clinical trials will be considered.
Cell cycle-related proteins (cyclins/cdks) : new targets for metabolic control. We have preliminary data indicating that some cyclins, such as cyclin D3, and cdks, such as cdk4, positively regulate the adipocyte differentiation process, and adipocyte function in a cell cycle-independent manner. We characterize the cross-talk between these proteins and PPARg which is the master regulator of adipogenesis. Furthermore, participation of cell cycle regulatory proteins in the control of pancreatic b-cell function is also being studied