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. In fact, many toxins, food additives and drugs are of small size, and could be involved in the worrying global increase of the incidence of immune-related diseases.
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 anti-inflammatory properties. Their advantage with regards to other immunotherapies such as monoclonal antibodies is their small size, which allows them to be administered orally, potentially increasing patient adherence. We are now in the process of 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 potential role of environmental, exogenous small molecules in the pathogeny of autoimmune diseases.
Sefina Arif; Iria Gomez-Tourino; Kamra Y, Pujol-Autonell I, Hanton E, Tree T, Melandri D, Hull C, Wherrett DK, Beam C, Roep BO, Lorenc A, Peakman M. GAD-Alum immunotherapy in type 1 diabetes expands bi-functional, Th1/Th2, autoreactive CD4 T cells. Diabetologia 2020. Jun;63(6):1186-1198.
Calviño-Sampedro C, Gomez-Tourino I, Cordero OJ, Reche PA, Gómez-Perosanz M, Sánchez-Trincado JL, Rodríguez MÁ, Sueiro AM, Viñuela JE, Calviño RV. (* Both authors contributed equally to this work). Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes. FASEB J. 2019 May;33(5):6390-6401.
Gomez-Tourino I, Kamra Y, Baptista R, Lorenc A, Peakman M. T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes. Nat Commun 2017 Nov 27;8(1):1792.
Brian D. Stadinski, Karthik Shekhar,Iria Gómez-Touriño, Jung J, Sasaki K, Sewell AK, Peakman M, Chakraborty AK, Huseby ES. Hydrophobic CDR3 residues promote the development of self-reactive T cells. Nat Immunol. 2016 Aug;17(8):946-55.
Cristina Calviño-Sampedro, Iria Gómez-Tourino, Varela-Calvino R, Cordero OJ. Apportioning blame: autoreactive CD4+ and CD8+ T cells in Type 1 Diabetes. Arch Immunol Ther Exp 2017 Jan 12; 65(4):275-284.
Gomez-Tourino I, Arif S, Eichmann M, Peakman M. T cells in type 1 diabetes: Instructors, regulators and effectors: A comprehensive review. J Autoimmun. 2016 Jan;66:7-16.
Iria Gómez-Touriño, Simón-Vázquez R, Alonso-Lorenzo J, Arif S, Calviño-Sampedro C, González-Fernández Á, Pena-González E, Rodríguez J, Viñuela-Roldán J, Verdaguer J, Cordero OJ, Peakman M, Varela-Calvino R. Characterization of the autoimmune response against the nerve tissue S100β in patients with type 1 diabetes. Clinical Exp Immunol. 2015 May;180(2):207-17.
Gómez-Touriño I, Sánchez-Espinel C, Hernández-Fernández A, González-Fernández A, Pena-González E, Rodríguez J, García-López JM, Varela-Calvino R. Galectin-1 synthesis in type 1 diabetes by different immune cell types: reduced synthesis by monocytes and Th1 cells. Cell Immunol. 2011; 271(2):319-28.
Gómez-Touriño I, Camiña-Darriba F, Otero-Romero I, Rodríguez MA, Hernández-Fernández A, González-Fernández A, Pena-González E, Rodríguez J, Rodríguez-Segade S, Varela-Calvino R. Autoantibodies to glial fibrillary acid protein and S100beta in diabetic patients. Diabet Med. Feb 2010; 27(2):246-8.
“Characterization of novel small molecules with anti-inflammatory capabilities for the treatment of rheumatoid arthritis (Halt!Inflamm)”. Spanish Ministry of Science and Innovation-Carlos III Institute of Health (Jan 2022-Dec 2024).