The dynamism and plasticity of energy metabolism is key to cellular homeostasis. Changes in metabolic processes are essential for a correct cellular function but also the basis of several pathologies. Its high relevance as a pharmacological target has emerged as a biomedical discipline in the intervention not only in chronic metabolic diseases but also in the potential correction of metabolic anomalies that are in the etiology of oncological and infectious diseases. The group focuses its research on the characterization of alterations in cellular energy metabolism due to infections, particularly by Leishmania parasites, and pathologies such as cancer. The signalling pathways involved are analyzed to identify new drug targets, working on the design and characterization of new molecules, as well as on the repositioning of existing drugs. The group also investigates the use of the energy metabolism of Leishmania as a pharmacological target, a pathogen in which the group has a long research trajectory.
Lima, M.L., Abengózar, M.A., Nácher-Vázquez, M., Martínez-Alcázar, M.P., Barbas, C., Tempone, A.G., López-Gonzálvez. A., Rivas, L. . Drug repurposing for Leishmania. Molecular basis of the leishmanicidal activity of the antidepressant sertraline. Antimicrobial Agents and Chemotheraphy. DOI: 10.1128/AAC.01928-18
Rivas, L., Nácher-Vázquez, M., Andreu, D. . Chapter 13: The Physical Matrix of the Plasma Membrane as a Target: The Charm of Drugs with Low Specificity. RSC Drug Discovery Series. 2018-January:248-281.
Martín-Sánchez, F., Martínez-García, J.J., Muñoz-García, M., Martínez-Villanueva, M., Noguera-Velasco, J.A., Andreu, D., Rivas, L., Pelegrín, P. . Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release. Cell death & disease. 8:e2984-.
Abengózar, M.A., Cebrián, R., Saugar, J.M., Gárate, T., Valdivia, E., Martínez-Bueno, M., Maqueda, M., Rivas, L. . Enterocin AS-48 as evidence for the use of bacteriocins as new leishmanicidal agents. Antimicrobial Agents and Chemotherapy. 61:-.
Contreras, L., Rial, E., Cerdan, S., Satrustegui, J. . Uncoupling Protein 2 (UCP2) Function in the Brain as Revealed by the Cerebral Metabolism of (1–13C)-Glucose. Neurochemical Research. 42:108-114.
Rodríguez-Sánchez, L., Rial, E. . The distinct bioenergetic properties of the human UCP1. Biochimie. 134:51-55.
Nicholls, D.G., Rial, E. . A novel regulatory mechanism for the brown-fat uncoupling protein?. Nature Structural and Molecular Biology. 23:364-365.
Fernandez-Prada, C., Vincent, I.M., Brotherton, M.-C., Roberts, M., Roy, G., Rivas, L., Leprohon, P., Smith, T.K., Ouellette, M. . Different Mutations in a P-type ATPase Transporter in Leishmania Parasites are Associated with Cross-resistance to Two Leading Drugs by Distinct Mechanisms. PLoS Neglected Tropical Diseases. 10:-.
Doménech, E., Maestre, C., Esteban-Martínez, L., Partida, D., Pascual, R., Fernández-Miranda, G., Seco, E., Campos-Olivas, R., Pérez, M., Megias, D., Allen, K., López, M., Saha, A.K., Velasco, G., Rial, E., Méndez, R., Boya, P., Salazar-Roa, M., Malumbres, M. . AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nature Cell Biology. 17:1304-1316.
Moreira, D., Rodrigues, V., Abengozar, M., Rivas, L., Rial, E., Laforge, M., Li, X., Foretz, M., Viollet, B., Estaquier, J., Cordeiro da Silva, A., Silvestre, R. . Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis. PLoS Pathogens. 11:1-24.
More recent Ph.D. Thesis
Juan Román Luque-Ortega. The energetic metabolisms in Leishmania as target for new leishmanicidal molecules . Complutense University of Madrid . June 2008
Maria Fernández-Reyes Silvestre. Molecular basis for the activity and resistance of membrane-active peptides in prokaryotes. Their comparison with Leishmania as eukaryotic model Complutense University of Madrid June 2010.
Daniela Saraiva Correa. Study of the bioenergetic alterations induced by synthetic compounds in Leishmania spp ,Sao Paolo State University August, 2014 . Co-supervised with Prof. André Gustavo Tempone.