Metabolism and Cell Signalling Group

Alejo Efeyan Group Leader
T +34 917328000 (Ext 3540)
aefeyan@cnio.es

Research Scientists

Bárbara Martínez

Post-Doctoral Fellows

Yurena Vivas

Graduate Students

Lucas Fellmann
Elena Fernández
Sofía García

Technicians

Jon Lasa
Alba Sanz

In the Metabolism & Cell Signalling Lab we study the links between nutrients, cancer and ageing. All our cells integrate signals emanating from the abundance of intracellular nutrients and the nutritional state of the entire organism. Integration of these signals is key to adjusting metabolic functions, as well as for energy storage and expenditure. Importantly, the components of these signalling cascades are generally corrupted in cancer, and are the drivers of metabolic complications of chronic nutrient overload. Conversely, dietary restriction regimes are extremely efficacious interventions against tumorigenesis and to delay the process of ageing; albeit we still ignore the fundamental molecular underpinnings of such protective effects. We combine mouse genetics and cell biological tools to gain insight into the genetic and environmental corruptions of nutrient signalling cascades, aiming to conceive therapeutic interventions in the context of cancer, obesity, and the process of ageing.

Recent publications

Zabala-Letona A, Pujana-Vaquerizo M, Martinez-Laosa B, Ponce-Rodriguez M, Garcia-Longarte S, Mendizabal I, Gimeno A, Rogalska M, Tan J, Cabrera D, van Liempd S, Ximenez-Embun P, Espinosa S, Fagoaga-Eugui M, Peccati F, Zakrzewski M, Astobiza I, Arana-Castañares M, Cherkaoui S, Sendino M, Martín-Barros I, Ercilla A, Bozal-Basterra L, Carlevaris O, Arruabarrena-Aristorena A, Pérez-Andrés E, Santamaría-Zamorano T, Ferrer-Bonsoms JA, Carazo F, Cieśla M, Lobato C, Seoane J, Martín-Martín N, Barrio R, Sutherland JD, Aransay AM, Falcón-Pérez JM, Martínez-Pastor B, Rubio A, Blanco FJ, Hogarty MD, Morscher RJ, Berra E, Serwa RA, Jiménez-Barbero J, Jiménez-Osés G, Efeyan A, Finley L, Lizcano JM, Muñoz J, Valcarcel J, Carracedo A. (2026). Polyamine-dependent metabolic shielding regulates alternative splicing. Nature (in press). CNIO Publication.
Lesbats J, Brillac A, Reisz JA, Mukherjee P, Lhuissier C, Fernández-Monreal M, Dupuy JW, Sequeira A, Tioli G, De La Calle Arregui C, Pinson B, Wendisch D, Rousseau B, Efeyan A, Sander LE, D'Alessandro A, Garaude J. (2025). Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses. Nature 640, 524-533. CNIO Publication.
Clarke TL, Cho HM, Ceppi I, Gao B, Yadav T, Silveira GG, Boon R, Martinez-Pastor B, Amoh NYA, Machin B, Bernasocchi T, Ashfaq D, Mendez J, Kamaliyan Z, Del Río Pantoja J, Rogines GS, Crowley BT, McGinn DE, Giunta V, Tran O, Zackai EH, Lan L, Zou L, Emanuel BS, McDonald-McGinn DM, Cejka P, Mostoslavsky R. (2025). ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome. Nat Cell Biol 27, 1006-1020. CNIO Publication.
Cabezudo S, Cuervo N, García-Martín C, López-Perrote A, Reglero C, Maqueda-Real A, González-Corpas A, Serna M, Megías D, Efeyan A, Park S, Llorca O. (2025). Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity. FEBS Open Bio 15, 1771-1788. CNIO Publication.
Plata-Gómez AB, de Prado-Rivas L, Sanz A, Deleyto-Seldas N, García F, de la Calle Arregui C, Silva C, Caleiras E, Graña-Castro O, Piñeiro-Yáñez E, Krebs J, Leiva-Vega L, Muñoz J, Jain A, Sabio G, Efeyan A. (2024). Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver. Nat Commun 15, 1878. CNIO Publication.
Rodriguez-Ramiro I, Pastor-Fernández A, López-Aceituno JL, Garcia-Dominguez E, Sierra-Ramirez A, Valverde AM, Martinez-Pastor B, Efeyan A, Gomez-Cabrera MC, Viña J, Fernandez-Marcos PJ. (2024). Pharmacological and genetic increases in liver NADPH levels ameliorate NASH progression in female mice. Free Radical Bio Med 210, 506-518. CNIO Publication.
Nikolic I, Ruiz-Garrido I, Crespo M, Romero-Becerra R, Leiva-Vega L, Mora A, León M, Rodríguez E, Leiva M, Plata-Gómez AB, Alvarez Flores MB, Torres JL, Hernández-Cosido L, López JA, Vázquez J, Efeyan A, Martin P, Marcos M, Sabio G (2024). Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis. EMBO Rep 25, 2635-2661. CNIO Publication.
Kumar EA, Korfi K, Bewicke-Copley F, Close K, Heward J, Witzig T, Leukam M, Ansell S, Scott J, Clear A, Efeyan A, Green M, Siebert R, Peck B, Calaminici M, Wang J, Smith S, Novak A, Fitzgibbon J, Okosun J. (2024). CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma. Br J Haematol 205, 1804-1809. CNIO Publication.
Ortega-Molina A, Lebrero-Fernández C, Sanz A, Calvo-Rubio M, Deleyto-Seldas N, de Prado-Rivas L, Plata-Gómez AB, Fernández-Florido E, González-García P, Vivas-García Y, Sánchez García E, Graña-Castro O, Price NL, Aroca-Crevillén A, Caleiras E, Monleón D, Borrás C, Casanova-Acebes M, de Cabo R, Efeyan A. (2024). A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan. Nature Aging 4, 1102-1120. CNIO Publication. Open Access
Pastor-Fernández A, Gómez de Las Heras MM, Escrig-Larena JI, Barradas M, Pantoja C, Plaza A, Lopez-Aceituno JL, Durán E, Efeyan A, Mittelbrunn M, Martinez L, Fernandez-Marcos PJ. (2024). Sexual dimorphism in the antitumor immune responses elicited by the combination of fasting and chemotherapy. Cancer Commun 44, 508-513. CNIO Publication.
Samson N, Bosoi CR, Roy C, Turcotte L, Tribouillard L, Mouchiroud M, Berthiaume L, Trottier J, Silva HCG, Guerbette T, Plata-Gómez AB, Besse-Patin A, Montoni A, Ilacqua N, Lamothe J, Citron YR, Gélinas Y, Gobeil S, Zoncu R, Caron A, Morissette M, Pellegrini L, Rochette PJ, Estall JL, Efeyan A, Shum M, Audet-Walsh É, Barbier O, Marette A, Laplante M. (2024). HSDL2 links nutritional cues to bile acid and cholesterol homeostasis. Sci Adv 10, eadk9681. CNIO Publication.
Kobialka P, Llena J, Deleyto-Seldas N, Munar-Gelabert M, Dengra JA, Villacampa P, Albinyà-Pedrós A, Muixi L, Andrade J, van Splunder H, Angulo-Urarte A, Potente M, Grego-Bessa J, Castillo SD, Vanhaesebroeck B, Efeyan A, Graupera M. (2023). PI3K-C2β limits mTORC1 signaling and angiogenic growth.. Sci Signal 16, eadg1913. Publication in other institutions.
Smirnov D, Eremenko E, Stein D, Kaluski S, Jasinska W, Cosentino C, Martinez-Pastor B, Brotman Y, Mostoslavsky R, Khrameeva E, Toiber D. (2023). SIRT6 is a key regulator of mitochondrial function in the brain. Cell Death Dis 14, 35. CNIO Publication.
Deleyto-Seldas N, Efeyan A. (2023). AMPK knocks at the gate of GATOR. Nat Metabolism 5, 197-198. CNIO Publication.
García-Lizarribar A, Villasante A, Lopez-Martin JA, Flandez M, Soler-Vázquez MC, Serra D, Herrero L, Sagrera A, Efeyan A, Samitier (2023). 3D bioprinted functional skeletal muscle models have potential applications for studies of muscle wasting in cancer cachexia. Biomater Adv 150, 213426. CNIO Publication. Open Access
Linder SJ, Bernasocchi T, Martínez-Pastor B, Sullivan KD, Galbraith MD, Lewis CA, Ferrer CM, Boon R, Silveira GG, Cho HM, Vidoudez C, Shroff S, Oliveira-Costa JP, Ross KN, Massri R, Matoba Y, Kim E, Rueda BR, Stott SL, Gottlieb E, Espinosa JM, Mostoslavsky R (2023). Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells. Nat Metabolism (in press). CNIO Publication. Open Access
Barradas M, Plaza A, Colmenarejo G, Lázaro I, Costa-Machado LF, Martín-Hernández R, Micó V, López-Aceituno JL, Herranz J, Pantoja C, Tejero H, Diaz-Ruiz A, Al-Shahrour F, Daimiel L, Loria-Kohen V, Ramirez de Molina A, Efeyan A, Serrano M, Pozo OJ, Sala-Vila A, Fernandez-Marcos PJ. (2022). Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity. Nat Commun 13, 5677. CNIO Publication. Open Access
Di Lorenzo G, Iavarone F, Maddaluno M, Plata-Gómez AB, Aureli S, Quezada Meza CP, Cinque L, Palma A, Reggio A, Cirillo C, Sacco F, Stolz A, Napolitano G, Marin O, Pinna LA, Ruzzene M, Limongelli V, Efeyan A, Grumati P, Settembre C. (2022). Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.. Sci Adv 8, eabo1215. CNIO Publication. Open Access
Fernández LP, Deleyto-Seldas N, Colmenarejo G, Sanz A, Wagner S, Plata-Gómez AB, Gómez-Patiño M, Molina S, Espinosa-Salinas I, Aguilar-Aguilar E, Ortega S, Graña-Castro O, Loria-Kohen V, Fernández-Marcos PJ, Efeyan A, Ramírez de Molina A. (2022). Folliculin-interacting protein FNIP2 impacts on overweight and obesity through a polymorphism in a conserved 3′ untranslated region. Genome Biol 23, 230. CNIO Publication. Open Access
Ong YT, Andrade J, Armbruster M, Shi C, Castro M, Costa ASH, Sugino T, Eelen G, Zimmermann B, Wilhelm K, Lim J, Watanabe S, Guenther S, Schneider A, Zanconato F, Kaulich M, Pan D, Braun T, Gerhardt H, Efeyan A, Carmeliet P, Piccolo S, Grosso AR, Potente M (2022). A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth.. Nat Metabolism 4, 672-682. CNIO Publication. Open Access
Vivas-García Y, Efeyan A (2022). The metabolic plasticity of B cells.. Front Mol Biosci 9, 991188. CNIO Publication. Open Access
de la Calle Arregui C, Plata-Gómez AB, Deleyto-Seldas N, García F, Ortega-Molina A, Abril-Garrido J, Rodriguez E, Nemazanyy I, Tribouillard L, de Martino A, Caleiras E, Campos-Olivas R, Mulero F, Laplante M, Muñoz J, Pende M, Sabio G, Sabatini DM, Efeyan A (2021). Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling. Nat Commun 12, 3660. CNIO Publication. Open Access
Pae J, Ersching J, Castro TBR, Schips M, Mesin L, Allon SJ, Ordovas-Montanes J, Mlynarczyk C, Melnick A, Efeyan A, Shalek AK, Meyer-Hermann M, Victora GD (2021). Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells. J Exp Med 218, e20201699. CNIO Publication.
Martinez-Pastor B, Silveira GG, Clarke TL, Chung D, Gu Y, Cosentino C, Davidow LS, Mata G, Hassanieh S, Salsman J, Ciccia A, Bae N, Bedford MT, Megías D, Rubin LL, Efeyan A, Dellaire G, Mostoslavsky R (2021). Assessing kinetics and recruitment of DNA repair factors using high content screens. Cell Reports 37, 110176. CNIO Publication. Open Access
Ortega-Molina A, Lebrero-Fernández C, Sanz A, Deleyto-Seldas N, Plata-Gómez AB, Menéndez C, Graña-Castro O, Caleiras E, Efeyan A (2021). Inhibition of Rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs.. Cell Reports 36, 109372. CNIO Publication. Open Access
Deleyto-Seldas N, Efeyan A. (2021). The mTOR-Autophagy Axis and the Control of Metabolism. Front Cell Dev Biol 9, 655731. CNIO Publication.
Spicer G, Gutierrez-Erlandsson S, Matesanz R, Bernard H, Adam AP, Efeyan A, Thompson S (2021). Harnessing DNA for nanothermometry. J BIOPHOTONICS 14, e202000341. CNIO Publication.
Ortega-Molina A, Efeyan A (2021). From mouse genetics to targeting the Rag GTPase pathway. Molecular Cellular Oncology 8, 1979370. CNIO Publication.
Plata-Gómez AB, Crespo M, de la Calle Arregui C, de Prado-Rivas L, Sabio G, Efeyan A (2021). Protocol for the assessment of mTOR activity in mouse primary hepatocytes. Star Protocols 2, 100918. CNIO Publication.