Category: Publications (Page 1 of 19)

Attack of the kinases: JNK signaling in metabolism

13/03/2026 / Sabio lab

Iara Fernández-González, Jane Jose Vattathara, Roger J. Davis, Guadalupe Sabio & Miguel López.

The global rise in obesity has become a major health concern, in part due to the easy availability and consumption of high-calorie foods together with an increasingly sedentary lifestyle.

More than a mere consequence of excess fat accumulation, obesity is now considered a complex health issue involving disrupted balance in how the body manages energy, primarily due to miscommunication between brain regions, such as the hypothalamus, and peripheral organs. One important aspect of this problem is how specific cell signaling pathways are disrupted by aberrant energy sensing and by oxidative stress-mediated damage and inflammation. Among these, AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) have gained wide attention as key players that integrate nutrient-, hormone- and inflammation-related signals.

Here, we provide a comprehensive review of isoform-specific JNK functions, highlighting recent advances in the understanding of JNK1, JNK2 and JNK3 in hypothalamic circuits that govern energy balance, thermogenesis and hepatic lipid metabolism. In addition, we also highlight the evolutionary and physiological significance of these kinase isoforms. Thus, this review encompasses current knowledge and key unanswered questions regarding the role of JNK in central and peripheral metabolic regulation.

Am J Physiol Regul Integr Comp Physiol. 2026 Feb 23. doi: 10.1152/ajpregu.00286.2025.

MicroRNA whole-blood profiling in hospitalized patients with candidemia identified miR-125a-5p and miR-99b-5p as potential biomarkers for Candida albicans bloodstream infection

04/11/2025 / Sabio lab

Silvio Ragozzino, Daniel Salete-Granado, Luis-Antonio Corchete, María-Paz Vaquero-Herrero, Edgar Bernardo, María Siller-Ruiz, Rebeca Sánchez González, Fabián Castaño-Romero, María-Ángeles Pérez-Nieto, Alicia García-Señán, Carlos Gutiérrez-Cerrajero, Cristina Carbonell, Jorge-Luis Torres, Rogelio González-Sarmiento, Guadalupe Sabio, Inmaculada García-García, Hugo-Guillermo Ternavasio-de la Vega, Maura Rojas-Pirela & Miguel Marcos.

Objectives: Analyze miRNA and mRNA expression in patients with bloodstream infection (BSI) caused by Candida albicans (CA) and non-albicans Candida spp. (CNA).

Patients/methods: We prospectively enrolled 20 adults with candidemia (10 CA and 10 CNA) and 22 hospitalized controls without sepsis but with comparable comorbidities. miRNA and mRNA expression were determined by next-generation sequencing (NGS), and differentially expressed miRNAs were validated by qPCR. Integrated miRNA–mRNA and KEGG/Reactome enrichment analyses were used to predict miRNA targets and identify perturbed pathways.

Differential RNA-Seq expression profiles of patients with *C. albicans* candidemia.

Results: NGS detected seven dysregulated miRNAs in CA vs. controls. qPCR confirmed marked overexpression of miR-125a-5p and miR-99b-5p in CA compared with CNA and controls. No miRNAs were differentially expressed between the CNA and control groups. RNA-Seq revealed that 22, 111, and 152 genes were differentially expressed in CA vs. controls, CNA vs. controls, and CA vs. CNA, respectively. Enrichment analysis highlighted cell-cycle and DNA-replication programs in both species groups, while CA uniquely affected histidine/phenylalanine metabolism. Integrated mapping linked upregulated miR-125a-5p to repression of pro-apoptotic and immune-modulatory genes, whereas miR-99b-5p targeted cell-cycle checkpoint genes.

Conclusions: Overexpression of miR-125a-5p and miR-99b-5p in whole blood may discriminate C. albicans candidemia. These miRNAs are promising rapid biomarkers and targets for antifungal therapy.

Int J Infect Dis (2025): 108148.

Cx43 enhances response to BRAF/MEK inhibitors by reducing DNA repair capacity

04/07/2025 / Sabio lab

Adrián Varela-Vázquez, Amanda Guitián-Caamaño, Paula Carpintero-Fernández, Alexander Carneiro-Figueira, Vanesa Álvarez, Marta Varela-Eirín, Teresa Calleja-Chuclá, Susana B. Bravo-López, Anxo Vidal, Juan Sendón-Lago, Marina Rodriguez-Candela Mateos, José R. Caeiro, Victoria Sanz-Moreno, Trond Aasen, Miguel G. Blanco, Guadalupe Sabio, María Quindós, Carmen Rivas, David Santamaría, Carlos Fernandez-Lozano, Eduardo Fonseca, Pablo Huertas, Berta Sánchez-Laorden, Constance Alabert & María D. Mayán

BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments.

Cx43 enhances senescence of primary tumours.

Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA damage and cellular senescence. The nuclear compartmentalization promoted by Cx43 contributes to genome instability and synthetic lethality caused by excessive DNA damage, which could provide a therapeutic approach for these tumours to overcome drug resistance. Based on these findings, we designed a drug combination using small extracellular vesicles (sEVs) to deliver the full-Cx43 in combination with the BRAF/MEKi.

This study reveals Cx43 as a regulator of DNA repair and BRAF/MEKi response, highlighting the therapeutic potential that this approach could eventually have in the clinic to overcome the limitations of current therapies and improve treatment outcomes for patients with advanced BRAF mutant tumours.

Nat Commun (2025); 16 (1): 6168.