Angel R. Nebreda obtained his PhD in Molecular Biology from the University of Salamanca (Spain) and then worked as a postdoc at the National Institutes of Health in Bethesda (USA) and the Cancer Research-UK Clare Hall Laboratories in South Mimms (UK). In 1995, he started his own group at the European Molecular Biology Laboratory in Heidelberg (Germany) where he worked for 9 years and then moved to the newly created Centro Nacional de Investigaciones Oncológicas in Madrid. He is currently an ICREA Research Professor at the Institute for Research in Biomedicine in Barcelona, where he leads a multidisciplinary team with expertise in biochemistry and molecular and cellular biology techniques, genetically modified mice and preclinical cancer models. He was elected EMBO member in 2003 and has obtained ERC Advanced and Proof of Concept grants.
Research interests
The group investigates how external signals are interpreted by cells to modulate their proliferation, differentiation and survival, focusing on protein kinases. Current work addresses the role of the p38 MAPK pathway in tumor development and chemoresistance mechanisms, either by regulating the fitness of the cancer cell or by controlling the cross talk between cancer cells and stromal cells in the tumor microenvironment. The experimental approach combines biochemical techniques and chemical tools with studies in established cell lines and primary cell cultures, as well as in vivo analyses using mouse models. Our goal is to identify therapeutic opportunities based on the modulation of p38 MAPK signaling. We are also performing screenings to find actionable targets that can be used to boost current therapeutic approaches and to design new targeted therapies for heterogeneous and chemoresistant tumors.
Selected publications
- Pous, J., Baginski, B., Martin-Malpartida, P., González, L., Scarpa, M., Aragon, E., Ruiz, L., Mees, R.A., Iglesias-Fernández, J., Orozco, M., Nebreda, A.R.* and Macias, M.J.* 2023, 'Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α', Nature Communications 14, 7920.
- González L, Díaz L, Pous J, Baginski B, Duran-Corbera A, Scarpa M, Brun-Heath I, Igea A, Martín-Malpartida P, Ruiz L, Pallara Ch, Esguerra M, Colizzi F, Mayor-Ruiz C, Biondi RM, Soliva R, Macias MJ, Orozco M & Nebreda AR 2023, 'Characterization of p38a autophosphorylation inhibitors that target the non-canonical activation pathway', Nature Communications, 14, 3318.
- Dan, Y., Radic , N., Gay , M., Fernández-Torras , A., Arauz , G., Vilaseca , M., Aloy, P., Canovas , B. and Nebreda, A.R. 2023, 'Characterization of p38a signaling networks in cancer cells using quantitative proteomics and phosphoproteomics', Molecular & Cellular Proteomics 22, 100527
- Cubillos-Rojas M, Loren G, Hakim YZ, Verdaguer X, Riera A* and Nebreda AR* (2023). 'Synthesis and Biological Activity of a VHL-Based PROTAC Specific for p38 alpha', Cancers 15, 611.
- Gonzalez, L., Domingo-Muelas, A., Duart-Abadía, P., Nuñez, M., Mikolcevic, P., Llonch, E., Cubillos-Rojas, M., Canovas, B., Forrow, S.M.A., Morante-Redolat, J.M., Fariñas, I.* and Nebreda, A.R.* (2023) 'The atypical CDK activator RingoA/Spy1 regulates exit from quiescence in neural stem cells', iScience 26, 106202.
- Sugioka, S., Yamada, H., Ishii, A., Kato, Y., Mori, K.P., Ohno, S., Handa, T., Ikushima, A., Ishimura, T., Osaki, K., Tokudome, T., Matsusaka, T., Nebreda, A.R., Yanagita, M., Yokoi, H. 2023, 'Dual deletion of guanylyl cyclase-A and p38 MAPK in podocytes with aldosterone administration causes glomerular intracapillary thrombi', Kidney International 104, 508-525.