Angel R. Nebreda

Institut de Recerca Biomèdica de Barcelona

Life & Medical Sciences

Angel R. Nebreda obtained his PhD in Biochemistry and Molecular Biology at 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 (Spain). He is currently an ICREA Research Professor at the Institute for Research in Biomedicine, in Barcelona (Spain). His research interests focus on mechanisms regulated by protein kinases in cell proliferation, differentiation and survival, particularly in relation to cancer. He was elected EMBO member in 2003 and is an Editor of FEBS Letters and the Biochemical Journal.

Research interests

We are investigating molecular mechanisms of tumorigenesis, specially regarding how the p38 MAPK signaling pathway regulates cell viability, proliferation and invasion, using a combination of biochemical approaches and studies in human cancer cell lines. An important question is how this signalling pathway contributes to the ability of tumor cells to bypass normal controls. We also use genetically modified mice, which allow the inactivation of this pathway in a regulated and tissue-specific manner, and chemical inhibitors to investigate physiological functions of p38 MAPKs and their role in lung, colon and breast cancer, as well as the connection between inflammation and tumorigenesis. We are very interested in the identification of therapeutic opportunities based on the modulation of p38 MAPK signaling. Moreover, we are studying the regulation and functions of a new family of proteins named RINGO that can activate the cell cycle kinases Cdk1 and Cdk2.

Selected publications

- Jaeger S, Igea A, Arroyo R, Alcalde V, Canovas B, Orozco M, Nebreda AR & Aloy P 2017, 'Quantification of pathway crosstalk reveals novel synergistic drug combinations for breast cancer', Cancer Research 77(2):459-469.

- Colie S, Sarroca S, Palenzuela R, Garcia I, Matheu A, Corpas R, Dotti CG, Esteban JA, Sanfeliu C & Nebreda AR 2017, 'Neuronal p38 alpha mediates synaptic and cognitive dysfunction in an Alzheimer's mouse model by controlling beta-amyloid production', Scientific Reports, 7, 45306.

- Kuzmanic A, Sutto L, Saladino G, Nebreda AR, Gervasio FL & Orozco M 2017, 'Changes in the free-energy landscape of p38 alpha MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations', Elife, 6, e22175.

- Salvador-Bernaldez S, Mateus SB, del Barco Barrantes I, Arthur SC, Martinez-A C, Nebreda AR & Salvador JM 2017, 'p38 alpha regulates cytokine-induced IFN gamma secretion via the Mnk1/eIF4E pathway in Th1 cells', Immunology and Cell Biology, 95, 9, 814 - 823.

- Trempolec N, Muñoz JP, Slobodnyuk K, Marin S, Cascante M, Zorzano A & Nebreda AR 2017, 'Induction of oxidative metabolism by the p38a/MK2 pathway', Scientific Reports 7:11367.

- Terriente-Félix A, Perez L, Bray SJ, Nebreda AR* & Milan M* 2017, 'Drosophila model of myeloproliferative neoplasm reveals a feed-forward loop in the JAK pathway mediated by p38 MAPK signaling', Disease Models & Mechanisms 10, 399-407

Selected research activities

Keynote speaker at LIII SAIB 2017 - Joint meeting of the Argentinean Societies for Research on Biosciences. November 2017. Buenos Aires, Argentina.