Biophysics of the Immune System is the research team leaded by Dr. Rubén Vicente. The main interest is understanding the role of ion fluxes and membrane composition regulation in the physiology of immune cells, having a special interest in calcium signalling, zinc fluxes and de novo ceramide synthesis. The current research projects are:
Calcium signaling and ORMDL3 pathophysiology
ORMDL3 is a transmembrane protein located in the endoplasmic reticulum. This protein has been shown to negatively regulate sphingolipid synthesis and to alter calcium homeostasis. As a consequence, alterations in ORMDL3 expression levels are associated to inflammatory diseases like asthma, inflammatory bowel diseases or rheumatoid arthritis. Our team is focus on studying the mechanistic insights of ORMDL3 cellular function.
Zinc signaling in immune cells
Zinc is a trace element essential for human health. Zinc deficiency is common in old adults, vegetarians and patients with chronic inflammatory diseases. This condition causes immune dysfunction leading to increased risk of inflammatory and infectious diseases. However, the specific role of zinc in the physiology of T-cells is still poorly characterized. Zinc is known to affect T lymphocyte maturation, differentiation and cytokine production. Our laboratory has demonstrated that zinc positively potentiates T-cell function by enhancing the three main signalling activation pathways, AP-1, NF-kB and NFAT1. In addition we have described that the Zip6 zinc transporter is essential for a proper T-cell activation. We aim to have a better knowledge on the signalling events that modulate zinc in T to understand the benefits and risks of a zinc-based nutritional immunity.
NanoTarg: a nanotechnological platform to treat cancer
Our team, together with the NanoMedicine lab leaded by Dr. Pilar Rivera, is involved in the development of NanoTarg, a novel nanotechnological platform to improve diagnosis and treatment of cancer. We have determined an oncotarget to specifically accumulate nanocapsules in the tumoral tissue and we are participating in the preclinical validation of the technology.
- Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R.(2010) The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet. 19, 111-21.
- Carreras-Sureda A, Cantero-Recasens G, Rubio-Moscardo F, Kiefer K, Peinelt C, Niemeyer BA, Valverde MA, Vicente R. (2013) ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Hum Mol Genet. 22:519-30.
- Engelken J, Carnero-Montoro E, Pybus M, Andrews GK, Lalueza-Fox C, Comas D, Sekler I, de la Rasilla M, Rosas A, Stoneking M, Valverde MA, Vicente R*, Bosch E*. (2014)Extreme population differences in the human zinc transporter ZIP4 (SLC39A4) are explained by positive selection in Sub-Saharan Africa. PLoS Genet. 10(2):e1004128. * both laboratories contributed equally
- Kiefer K, Carreras-Sureda A, García-López R, Rubio-Moscardó F, Casas J, Fabriàs G, Vicente R. (2015) Coordinated regulation of the orosomucoid-like gene family expression controls de novo ceramide synthesis in mammalian cells. J Biol Chem. Jan 30;290(5):2822-30. doi: 10.1074/jbc.M114.595116. Epub 2014 Dec 17.
- Orta-Mascaró M, Consuegra-Fernández M, Carreras E, Roncagalli R, Carreras-Sureda A, Alvarez P, Girard L, Simões I, Martínez-Florensa M, Aranda F, Merino R, Martínez VG, Vicente R, Merino J, Sarukhan A, Malissen M, Malissen B, Lozano F. (2016) CD6 modulates thymocyte selection and peripheral T cell homeostasis. J Exp Med. Jul 25;213(8):1387-97. doi: 10.1084/jem.20151785. Epub 2016 Jul 4.
- Carreras-Sureda A, Rubio-Moscardo F, Olvera A, Argilaguet J, Kiefer K, Mothe B, Meyerhans A, Brander C, Vicente R. Lymphocyte Activation Dynamics Is Shaped by Hereditary Components at Chromosome Region 17q12-q21. PLoS One. 2016 Nov 11;11(11):e0166414. doi: 10.1371/journal.pone.0166414.
- Matalonga J, Glaria E, Bresque M, Escande C, Carbó JM, Kiefer K, Vicente R, León TE, Beceiro S, Pascual-García M, Serret J, Sanjurjo L, Morón-Ros S, Riera A, Paytubi S, Juarez A, Sotillo F, Lindbom L, Caelles C, Sarrias MR, Sancho J, Castrillo A, Chini EN, Valledor AF. (2017) The Nuclear Receptor LXR Limits Bacterial Infection of Host Macrophages through a Mechanism that Impacts Cellular NAD Metabolism. Cell Rep. 2017 Jan 31;18(5):1241-1255. doi: 10.1016/j.celrep.2017.01.007.
- Colomar N, Meseguer A, Company I, Jutz S, Olvera A, Kiefer K, Brander C, Herrera-Fernández V, Steinberger P and Vicente R. Zip6 transporter is an essential component of the lymphocyte activation machinery. J. Immunol 2019 Jan 15;202(2):441-450. doi: 10.4049/jimmunol.1800689
- Kiefer K, Casas J, García-López R, Vicente R. Ceramide Imbalance and Impaired TLR4-Mediated Autophagy in BMDM of an ORMDL3-Overexpressing Mouse Model. Int J Mol Sci. 2019 Mar 20;20(6). doi: 10.3390/ijms20061391.
- Carreras-Sureda A, Jaña F, Ramos-Fernández E, Urra H, van Vliet AR, Durand S, Mortenson D, Pihan P, Gonzalez-Quiroz M, Vicente R, Inestrosa N, Wiseman L, Agostinis P, Bultynck G, Court F, Kroemer G, Cárdenas JC and Hetz C. Non-canonical function of the unfolded protein response sensor IRE1α as a structural determinant of mitochondrial-associated ER membranes Nat Cell Biol 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y.