Nuclear Receptors in metabolism, immune responses and cancer

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.