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. Current interests of the group include 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 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 very 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

– Batlle R, Andres E, Gonzalez L, Llonch E, Igea A, Gutierrez-Prat N, Berenguer-Llergo A & Nebreda AR  2019, ‘Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38alpha through TGF-beta and JNK signaling‘, Nature Communications, 10, 3071.

– Slobodnyuk K, Radic N, Ivanova S, Llado A, Trempolec N, Zorzano A & Nebreda AR 2019, ‘Autophagy-induced senescence is regulated by p38alpha signaling‘, Cell Death & Disease, 10, 376.

– Navarrete M, Cuartero MI, Palenzuela R, Draffin JE, Konomi A, Serra I, Colie S, Castano-Castano S, Hasan MT, Nebreda AR & Esteban JA, Jose A 2019, ‘Astrocytic p38alpha MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory‘, Nature Communications, 10, 2968.

– Martin-Segura A, Casadome-Perales A, Fazzari P, Mas JM, Artigas L, Valls R, Nebreda AR & Dotti CG 2019, ‘Aging Increases Hippocampal DUSP2 by a Membrane Cholesterol Loss-Mediated RTK/p38MAPK Activation Mechanism‘, Frontiers In Neurology, 10, 675.

– Moreno-Cugnon L, Revuelta M, Arrizabalaga O, Colie S, Moreno-Valladares M, Jimenez-Blasco D, Gil-Bea F, Llarena I, Bolaños JP, Nebreda AR & Matheu A 2019, ‘Neuronal p38alpha mediates age-associated neural stem cell exhaustion and cognitive decline‘, Aging Cell 18, e13044

– Eftekharzadeh B, Banduseela VC, Chiesa G, Martínez-Cristóbal P, Rauch JN, Schwarz DMC, Shao H, Marin-Argany M, Di Sanza C, Giorgetti E, Yu Z, Pieratelli R, Felli IC, Brun-Heath I, García J, Nebreda AR, Gestwicki JE, Lieberman AP & Salvatella X 2019, ‘Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor, Nature Communications 10, 3562.