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 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 for Rheumatoid Arthritis and Type 1 Diabetes, and in vivo in mouse models, as a previous step to proceeding to preclinical and clinical trials.
We also work in understanding the molecular mechanisms driving autoimmune diseases, in particular identifying novel T-cell antigens and T-cell receptor features which constitute biomarkers of Type 1 Diabetes. We are currently going a step further, investigating the role of small molecules as autoantigens for MAIT cells in autoimmune diseases.
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Liñas de investigación
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Membros
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Publicacións seleccionadas
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Resultados seleccionados
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Proxectos
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Patentes
Liñas de investigación
- 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.
- 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.
Membros
Publicacións seleccionadas
Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes
PLGA-PEI nanoparticle covered with poly(I:C) for personalised cancer immunotherapy.
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
Resultados seleccionados
- Study of mechanisms of autoimmunity: we recently showed that autoreactivity might have a physiological role in health, favouring thymic selection of autoantigen-specific T cells, and that this reactivity against self combines with pathogenic self-reactivity in patients with Type 1 Diabetes (T1D) (Nat Commun 2024). We also showed, for the first time, that thymic rearrangement events are abnormal in T1D, generating a TCR repertoire enriched in self-reactive features. Our most recent work in autoantigen identification, focused on metabolites and MAIT cells in T1D, has gained considerable attention in national and international congresses, including a plenary talk at the European Congress of Immunology (Dublin, 2024), and one of the best posters in the congress of the Immunology of Diabetes Society (Brugges, 2024).
- Identification and characterization of novel anti-inflammatory small molecules for the treatment of autoimmune diseases: we identified, through an unbiased high-throughput screening, 27 small molecules with previously unknown anti-inflammatory capabilities, specifically inhibiting the secretion of proinflammatory cytokines, and including both repurposing and novel molecules. We have validated and prioritized them based upon their effects on primary cells from patients with rheumatoid arthritis. Our work has been selected for oral presentation in the most renowned congresses of the field, including European League against Rheumatism (EULAR) congress (Milan 2023), congress of the Immunology of Diabetes Society (Paris, 2023), and European Congress of Immunology (Dublin, 2024). A patent and a publication are currently underway.
Proxectos
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Funding by Juvenile Diabetes Research Foundation (JDRF, EEUU)
Proxectos nacionais
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