Nuclear Receptors in metabolism, immune responses and cancer

Institute of Biomedicine (IBUB)

Annabel Valledor
Associate Professor-Serra Hunter Program
Dpt. of Cell Biology, Physiology and Immunology
School of Biology, University of Barcelona
Av. Diagonal, 643. Margalef Building, 3rd floor
08028-Barcelona, Spain
Phone: +34-934039384
E-mail: afernandezvalledor@ub.edu           Web

Carme Caelles
Associate Professor
Dpt. of Biochemistry & Physiology
School of Pharmacy and Food Sciences, University of Barcelona
Av. Joan XXIII, 27-31, Building B, 2nd floor
08028-Barcelona, Spain
Phone: +34-934037130
E-mail: ccaelles@ub.edu                                Web

Posdoctoral fellow: Joan Carles Rodríguez Rubio
PhD students: Carles Bayod Girón • Joan Font Díaz • Estibaliz Glaría Percaz • Nicole Letelier Torres • Melisa Morcillo Sánchez

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Current
Research

Nuclear receptors are a family of ligand-activated transcription factors that regulate development and physiology. In particular, we focus our research on a set of nuclear receptors, including the liver X receptors (LXRs), the peroxisome-proliferator activated receptors (PPARs) and the glucocorticoid receptor (GR), which have key roles in the modulation of immune responses, in metabolism, and in tumor development. In addition, agonists for GR and PPARs are used in the clinic for several disorders, and ligands for other nuclear receptors are intensively studied due to their therapeutic potential.

One of our research lines is the study of the biological roles of LXRs, which are activated by specific oxidized forms of cholesterol (oxysterols) and metabolites of the cholesterol biosynthetic pathway. Two isoforms of LXR have been identified, LXR-a and LXR-b. LXRs are key regulators of lipid and glucose homeostasis and also play an important role in the regulation of immune and inflammatory responses. We are interested in further exploring the roles of LXRs in the immune response and in the development of diseases with an inflammatory origin.

We also study the interaction of GR, LXRs and PPARs with other signal transduction pathways, particularly the c-Jun N-terminal kinase (JNK) pathway. The JNK pathway plays key roles in the induction of inflammatory responses and in obesity-associated insulin resistance, and its activation is counteracted by several nuclear receptors. We focus on the molecular mechanisms underlying this interaction, which may help improve the therapeutic profile of currently available drugs and/or identify novel targets for pharmacological intervention.

Selected
Publications

Matalonga, J.; Glaria, E.; Bresque, M.; Escande, C.; Carbó, J.M.; Kiefer, K.; Vicente, R.; León, T.E.; Beceiro, S.; Pascual-García, M.; Serret, J.; Sanjurjo, L.; Morón-Ros, S.; Riera, A.; Paytubi, S.; Juarez, A.; Sotillo, F.; Lindbom, L.; Caelles, C.; Sarrias, M.R.; Sancho, J.; Castrillo, A.; Chini, E.N.; Valledor, A.F. The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism. Cell Rep.18:1241-1255, 2017. doi: 10.1016/j.celrep.2017.01.007.

Pascual-García,M., Rue, L.; León, T.; Julve, J.; Carbó, J.M.; Matalonga, J.; Auer, H.; Celada, A.; Escolà-Gil, J.C.; Steffensen, K.R.; Pérez-Navarro; E.; Valledor, A.F. Reciprocal negative crosstalk between Liver X receptors and STAT1: effects on IFN-g-induced inflammatory responses and LXR-dependent gene expression. J. Immunol. 190:6520-6532, 2013. doi: 10.4049/jimmunol.1201393.

Lanuza-Masdeu, J.; Arévalo, M.I.; Vila, C.; Barberà, A.; Gomis, R.; Caelles, In vivo JNK activation in pancreatic b-cells leads to glucose intolerante caused by insulin resistance in páncreas. Diabetes 62:2308-2317, 2013. doi: 10.2337/db12-1097.

Pascual-García, M.; Carbó, J.M.; León, T.; Matalonga, J.; Out, R.; Van Berkel, T.J.; Sarrias, R.M.; Lozano, F.; Celada, A.; Valledor, A.F. Liver X receptors inhibit macrophage proliferation through downregulation of cyclins D1 and B1 and cyclin-dependent kinases 2 and 4. J. Immunol. 186:4656-4667, 2011. doi: 10.4049/jimmunol.1000585.

Díaz-Delfín, J.; Morales, M.; Caelles, C. Hypoglycemic action of thiazolidinediones/peroxisome proliferator-activated receptor gamma by c-Jun NH2-terminal kinase pathway. Diabetes 56:1865-1871.

Selected
Publications