International Protease Network

Laboratory of Molecular Genetics, DIBIT, Universit‡ Vita Salute San Raffaele and
IFOM (FIRC Institute of Molecular Oncology)
Milan, Italy
Email: blasi.Francesco@hsr.it
Tel: +39 02 2643 4744
Fax: +39 02 2643 4844
Homepage: http://www.sanraffaele.org/research/blasi/

Research

We are interested in the Receptor (uPAR) for the urokinase plasminogen activator (uPA). In particolar we are studying its role in cell signaling as well as specific structural properties. In particular, we are interested in connecting the subcellular localization of uPAR with its specific functions. Since uPAR is a GPI-anchored protein, we are interested to determine the role of lipid rafts on uPAR properties, ie 1. enhancement of plasmin generation by pro-uPA activation; 2. affinity for its other ligand, vitronectin and role on adhesion; 3. ability to be cleaved by uPA and hence de-sensitization; 4. internalization and degradation of the uPA-PAI-1 complex; 5. specific signaling interactions with integrins, G-protein coupled receptors, tyrosine kinase receptors, etc.
Recently one particular aspect that concentrates our attention is the possible direct role of uPAR in oncogenesis. We are exploring this possibility by identifying specific functions of uPAR in cell proliferation and by analyzing the cooperation of uPAR with activated oncogenes or suppressor genes at both the cellular and organism level.

Collaborations

Nicolai Sidenius, PhD
Roberta Mazzieri, PhD
Orla Cunningham, PhD
Federico Furlan, MD
AnnaPaola Andolfo, PhD
Massimo Resnati, Biologist
Maria Macaren Sahores, PhD student

Publications

Orla Cunningham, Annapaola Andolfo, Maria Lisa Santovito, Francesco Blasi and Nicolai Sidenius. Differential lipid raft partitioning of the urokinase receptor regulates its biological functions and is controlled by receptor dimerization. EMBO J. 22, 5994-6003, 2003.

Blasi, F. and Carmeliet, P. uPAR: a versatile signaling orchestrator. Nature Rev. Mol. Biol. 3, 932-943, 2002.

Sidenius, N., Andolfo, A., Fesce, R. and Blasi, F. Urokinase regulates vitronectin binding in vitro and in vivo by controlling urokinase receptor oligomerization. J. Biol. Chem., 277, 27982-27990, 2002.

Resnati, M. , Pallavicini, I. , Wang, J.M., Oppenheim, J., Serhan, C.N., Romano, M. e Blasi, F. The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proc. Natl. Acad. Sci. U.S.A. 99, 1359-1364, 2002.

Degryse, B., Orlando,S., Resnati, M., Rabbani, S.A. and Blasi,F. Urokinase/Urokinase Receptor and Vitronectin/v3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways. Oncogene, 20, 2032-2043, 2001.