Immunity and Small Molecules
Our lab is focused in understanding the molecular mechanisms of autoimmunity, and how small molecules could be involved in both fostering and/or disrupting the functioning of the immune system. They constitute powerful drugs as they easily cross cell membranes, increasing the number of druggable targets but, at the same time, their small size and chemical features make them a potential source of immune disruption.
We have extensive experience and expertise in both basic and translational research, as well as in animal models of autoimmunity, and we previously identified a portfolio of novel and repurposed small molecules with previously unknown immunomodulatory properties. Their advantage with regards of other immunotherapies is their small size, which allows them to be administered orally, potentially increasing patient adherence. We are currently validating them ex vivo in Rheumatoid Arthritis and Type 1 Diabetes patients, and in vivo in mouse models, as a previous step to proceeding to preclinical and clinical trials.
We have also extensively worked in studying the molecular mechanisms driving autoimmune diseases, in particular identifying novel T-cell epitopes and T-cell receptor features which constitute biomarkers of the disease. We now aim to go a step further, looking for the role of small molecules as autoantigens for MAIT cells in autoimmune diseases.
- Identification and characterization of novel anti-inflammatory small molecules for the treatment of autoimmune diseases: in this translational research line we apply our knowledge in small molecules and immunity to develop novel drugs for the treatment of autoimmune diseases, through ex vivo and in vitro validation, in vivo models and chemoproteomics.
- Study of mechanisms of autoimmunity: in this research line we focus in disentangling the mechanisms that drive autoimmunity at the molecular level, namely identifying the nature of autoantigens, either peptidic or small molecules, quantifying the frequency of autoreactive cells in health and disease, and profiling the repertoire of T cell receptors, to gain a deeper understanding of the altered molecular mechanisms and to identify biomarkers of disease appearance and progression.
Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists.
GAD-Alum immunotherapy in type 1 diabetes expands bi-functional, Th1/Th2, autoreactive CD4 T cells
Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes
T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes.
Hydrophobic CDR3 residues promote the development of self-reactive T cells
T cells in type 1 diabetes: Instructors, regulators and effectors: A comprehensive review