Group Leader Associate Researchers Postdoctoral Predoctoral Technicians

Santos Mañes Brotón Emilia Mira Dámaso Rosa Ana Lacalle Blanco Lourdes Planelles Carazo Concepción Gómez-Moutón Alicia González Martín Manuel Tardáguila Sancho Araceli García Castro Rosa Mª Peregil Alcocer

SIGNALING NETWORKS IN INFLAMMATION AND CANCER Inflammation is a defensive response of an organism to tissue injury by internal or external stimuli. In homeostasis, inflammation is an important step in the adaptive immune response; however, deregulation of the inflammatory response could lead to autoimmunity or promote cancer. The transmigration of leukocytes from the bloodstream into inflamed tissues is a crucial step in the inflammatory response. To initiate transmigration, leukocytes must change their shape and adhesion properties, becoming functionally and spatially polarized. Leukocyte polarization is induced by guidance cues provided by the target tissue, which tell the cell where to go and when to stop. Our understanding of leukocyte polarization at the molecular level has progressed greatly in the last decade, including the discovery of key signaling pathways involved in this step.  Nonetheless, there are important questions that remain unanswered. In the coming years, our research will focus on three interrelated topics: 4. To understand how signaling pathways involved in leukocyte polarization communicate and coordinate with one other during inflammatory cell migration. 5.  To identify leukocyte signaling pathways aberrantly over-activated in chronic inflammatory diseases. 6. To identify key molecules that will most specifically inhibit the trafficking of cell subset that drive disease processes. Although the group is interested in inflammation as a process, much of our research is focused in the inflammatory response associated to tumor progression. .

Figure 1. Multiple interactions between inflammatory cells control tumor growth and metastasis. For detailed information visit: www.cnb.csic.es/~smanes/

SELECTED PUBLICATIONS Mañes, S., del Real, G., Martínez-A., C. 2003. Nature Rev. Immunol. 3: 557-568. Mañes, S., Mira, E., Colomer, R., Montero, S., Real, L.M., Gómez-Moutón, C., Jiménez-Baranda, S., Garzón, A., Lacalle, R.A., Harshman, K., Ruíz, A., Martínez-A., C. 2003. J. Exp. Med. 198:1381-1389. Molon, B., Gri, G., Betella, M., Gómez-Moutón, C., Lanzavecchia A., Martínez-A., C., Mañes, S.*, Viola, A.* 2005. Nature Immunol. 6: 465-471.  (* Co-corresponding authors). Jiménez-Baranda, S., Gómez-Moutón, C., Rojas, A., Martínez-Prats, L., Mira, E., Lacalle, R.A., Valencia,A., Dimitrov, D.S., Viola, A., Delgado, R., Martínez-A., C., Mañes, S. 2007. Nature Cell Biol. 9: 838-846. Lacalle, R.A., Peregil, R.M., Albar, J.P., Merino, E., Martínez-A., C., Mérida, I., Mañes, S. 2007. J. Cell Biol. 179: 1539-1553.