Our research focuses on trying to understand the mechanism of chemokine function.  This family of proteins is involved in a broad array of biological responses ranging from cell polarization, cell movement, immune and inflammatory responses.  Studies of chemokine signaling show that they stabilize different receptor conformations, which in turn defines distinct cell functions.  The chemokines also activate a tyrosine kinase pathway that shares many components with the biochemical pathway activated by the cytokine receptors.

    A cursory glance at chemokines and their receptors would suggest that their responses should be relatively simple to block, particularly considering that chemokine receptors belong to the GPCR family, among the most widespread and successful in today’s armamentarium of therapeutic targets.  Blocking chemokine action has nonetheless proved to be a complex task, and results of in vitro strategies often vary when applied in vivo.  Our interest is thus centered on studying chemokine immunobiology, to try to provide a clearer understanding of how this family of proteins acts, and to define new orientations for the treatment of many inflammatory and infectious diseases.

As the monomeric receptor was classically considered the functional conformation, most antagonists have been designed to block the binding site.  It is now clear, however, that chemokine receptors act as dimeric and even as oligomeric entities; analysis of the conformations adopted by these receptors at the cell membrane is therefore a prerequisite for understanding the function of these inflammatory mediators.  This is a critical question, as there are more than 25 receptors that bind more than 40 chemokines with similar affinities, and a single cell can express several receptors simultaneously.

Our aim is to analyze the chemokine receptor conformations at the cell surface, to determine which receptor combinations form homo- and/or heterodimers, to study their dynamic, to determine the functional consequences of stabilizing a specific conformation, and to establish the function of each conformation in vivo.  We will also analyze the chemokine-mediated signaling events, in particular the activation of the JAK/STAT pathway and its functional relevance. 

Department of Immunology and Oncolgy.

Centro Nacional de Biotecnología/CSIC

c/Darwin, 3. Campus UAM. 

MasterSwitch Project