CV Science

Arnaud Besson PhD in Molecular and Cellular Biology

Course and current status

-January 2011-present: Principal Investigator, Cancer Research center of Toulouse, CRCT INSERM UMR1037, CNRS ERL5294, Toulouse, France.

-January 2007-December 2010: Principal Investigator, CNRS. ATIP Group. Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, UMR 5088, Université Paul Sabatier-Toulouse III, Toulouse, France.

-July 2001-December 2006: Postdoctoral Training with Dr J. M. Roberts, Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.

-May 1997-June 2001: Ph.D. Training with Dr V. W. Yong, Departments of Oncology and Clinical Neuroscience, University of Calgary, Calgary, Canada.

-October 1995-March 1997: M.Sc Training with Dr R. L. Margolis, Laboratoire des Protéines du Cytosquelette, Institut de Biologie Structurale, CEA-CNRS, Grenoble, France.

Scientific summary

Cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family are tumor suppressors due to their ability to block cellular proliferation in the nucleus. However, increasing evidence indicate that CKIs also have cyclin-CDK independent functions, that are potentially oncogenic.

We found that p27 regulates actin cytoskeleton dynamics and cell migration through the modulation of RhoA activity. By binding RhoA, p27 prevents the interaction of RhoA with its activators, the guanine nucleotide exchange factors (GEFs). To assess the importance of these novel functions in vivo, we generated knock-in mice with a p27 gene carrying specific point mutations that abolish its ability to interact with cyclins-CDKs (p27CK-). The p27CK- allele dominantly caused an increase in spontaneous tumorigenesis in multiple organs, including the lung, compared to wild-type or p27-/- animals. In the lung, we found that tumors arising in p27CK- mice likely originated from the aberrant expansion of a bronchioalveolar stem cell pool. We are exploring the mechanism of these novel p27 functions and investigate their importance in cancer. We are also expanding our studies to the CKI p57Kip2.The main goal of the proposed research is to determine whether CKIs act as tumor suppressors by restricting the activities of cyclin-CDK complexes, but also as oncogenes, possibly through the regulation of cytoskeletal dynamics and stem cell fate, and to determine the mechanisms involved.

The projects developed in the lab include:

-To define the molecular mechanism by which p27 regulates Rho signaling and its involvement in tumorigenesis.

-Study the cyclin-CDK independent role of p27 during mitosis and cytokinesis.

-To determine the roles of p27 in bronchio-alveolar stem cell regulation.

-To investigate the cyclin-CDK independent functions of p57Kip2.