Angel R. Nebreda

Angel R. Nebreda

Institut de Recerca Biomèdica de Barcelona

Life & Medical Sciences

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, as well as in 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

We investigate mechanisms that allow cells to interpret stress signals and elaborate the appropriate responses. Our work focuses on signal integration by p38 MAPKs, addressing physiological functions and their roles in tumorigenesis. The main interests of the group are cancer cell homeostasis and chemoresistance mechanisms, the cross talk between cancer cells and stromal cells, and targeted therapies. We use a combination of biochemical approaches and studies with both established cell lines and primary cell cultures, as well as in vivo experiments using genetically modified mice, which allow the regulation of p38 MAPK signaling in a tissue-specific manner. We are interested in the identification of therapeutic opportunities based on the modulation of p38 MAPK activity using chemical compounds. Moreover, we study the regulation and functions of the RINGO proteins, a family of atypical activators of the cell cycle kinases Cdk1 and Cdk2.

Selected publications

- Vitos-Faleato, Jessica; Real, Sebastian M.; Gutierrez-Prat, Nuria; Villanueva, Alberto; Llonch, Elisabet; Drosten, Matthias; Barbacid, Mariano; Nebreda, Angel R. 2020, 'Requirement for epithelial p38alpha in KRAS-driven lung tumor progression', Proceedings of the National Academy of Sciences of the United States of America, 117, 2588 - 2596.

- Arriazu, Elena; Vicente, Carmen; Pippa, Raffaella; Peris, Irene; Martinez-Balsalobre, Elena; Garcia-Ramirez, Patricia; Marcotegui, Nerea; Igea, Ana; Alignani, Diego; Rifon, Jose; Mateos, Maria C.; Cayuela, Maria L.; Nebreda, Angel R.; Odero, Maria D. 2020, 'A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia', Blood Cancer Journal, 10, 3.

- Donoghue, Craig; Cubillos-Rojas, Monica; Gutierrez-Prat, Nuria; Sanchez-Zarzalejo, Carolina; Verdaguer, Xavier; Riera, Antoni; Nebreda, Angel R. 2020, 'Optimal linker length for small molecule PROTACs that selectively target p38 alpha and p38 beta for degradation', European Journal of Medicinal Chemistry, 201, 112451.

- Gonzalez, Laura; Nebreda, Angel R. 2020, 'RINGO/Speedy proteins, a family of non-canonical activators of CDK1 and CDK2', Seminars in Cell & Developmental Biology, 107, 21 - 27.

- Urosevic, Jelena; Blasco, Maria Teresa; Llorente, Alicia; Bellmunt, Anna; Berenguer-Llergo, Antoni; Guiu, Marc; Cañellas, Adriá; Fernandez, Esther; Burkov, Ivan; Clapés Cabrer, Maria; Cartañá, Mireia; Figueras-Puig, Cristina, Batlle, Eduard; Nebreda, Angel R.; Gomis, Roger R. 2020, 'ERK1/2 signaling induces upregulation of ANGPT2 and CXCR4 to mediate liver metastasis in colon cancer', Cancer Research, 80, 4668 - 4680.

Selected research activities

Patent application on compounds that modulate p38alpha autophosphorylation (WO2020120576).