Ramón Merino obtained the MD degree in June 1985 at the University of Cantabria (UC). From April 1986-April 1992, he performed a predoctoral training in Professor Shozo Izui's laboratory at the Department of Pathology, University of Geneva (Switzerland), studying immunopathogenic mechanisms responsible for the development of systemic lupus erythematosus. In March 1991, he obtained the PhD degree from the University of Geneva. From September 1992-November 1995, he performed a first postdoctoral training in Professor Gabriel Núñez's laboratory at the University of Michigan (USA), studying the genetic regulation of apoptosis in lymphocytes. From December 1995-March 1999, he carried out a second postdoctoral period in Professor Juan M. Hurlé's laboratory at the UC, characterizing the role of TGFβsuperfamily members during embryonic limb development. Since April 1999, he lead a research group, first at the Marqués de Valdecilla University Hospital (FIS Researcher), then at the UC (Ramón y Cajal Researcher) and since 2006 at the CSIC (Staff Scientist). His most recent work allowed the identification a new mechanism, regulated by BAMBI (BMP and Activin membrane-bound inhibitor), controlling the functional differentiation of CD4+ T lymphocytes into Tregs and Th17 subpopulations. Likewise, they defined BAMBI as a new therapeutic target in autoimmunity and developed anti-BAMBI monoclonal antibodies with therapeutic effects in autoimmune diseases. His research has been funded through grants from competitive Public Agencies and private Foundations. He is the author of 102 publications, most of them in Journals from first quartile of their specialties such as Nat. Cell. Biol., Proc. Natl. Acad. Sci. USA, J. Exp. Med. J. Clin Invest. EMBO J., Development, J. Immunol., Arthritis Rheum, and two international patents. He supervised 13 Doctoral Theses and 7 Master's Thesis.
Chronic Inflammatory and Autoimmune Diseases
Research lines
Our research project addresses the role of BAMBI (BMP and Activin Membrane-Bound Inhibitor), a plasma membrane-bound inhibitor of TGFβ signaling, in the control of Immune System activity. We have previously demonstrated that BAMBI forms part of a rheostat-like molecular device that through the direct regulation of TGFβ signalling strength and the indirect control of IL-2 signalling, influences the capacity of newly activated CD4+ T cells to functionally differentiate into anti-inflammatory regulatory T cells (Treg) and pro-inflammatory Th17 cells. In this regard, BAMBI deficiency protects mice against the development of autoimmune arthritis by Treg- and TGFβ-dependent mechanisms. Based in these findings, we have developed an inhibitory anti-mouse and anti-human BAMBI mAb, clone B101-37, that exhibits preventive and therapeutic activities in different experimental murine models of psoriasis and arthritis. This technology has been protected by a patent, owned by the CSIC and the Universidad de Cantabria that has been licensed to Inhibitec-Anticuerpos S.L., a recently created start-up company that plans to position B101.37 as a new gold standard in the management of psoriatic arthritis. Our present research activity is:
- To explore the role of BAMBI in mucosal immunity and microbiota composition and its possible involvement in in the development of inflammatory bowel disease and colon cancer associated to chronic inflammation.
- The role of BAMBI in humoral immune responses.
- In the context of Inhibitec-Anticuerpos, we plan to humanize B101-37 as a first step to its introduction into clinical trials.
From a technological point of view, our research group has a large experience in the induction and clinical and immunological study of several murine models of autoimmune/inflammatory diseases including systemic lupus erythematosus, collagen type-II induced autoimmune arthritis, Imiquimod-induced psoriasis, Saccharomyces Cerevisiae mannan-induced psoriatic arthritis and dextran sodium sulphate-induced colitis.
Patents
1- Title: Anticuerpos monoclonales frente a BAMBI y uso para tratamiento de enfermedades inflamatorias. International Patent PCT/ES2016/070852. Extended to EC (16870040.9), USA (060418INTEFSW00000022090528).
Inventors: Jesús Merino Pérez; Ramón Merino Pérez.
Owners: Consejo Superior de Investigaciones Científicas/Universidad de Cantabria.
2- Title: Methods for treating and diagnosing disease. Patente Internacional WO 2012/113785.
Inventors: Juan Saus; Fernando Revert; Ramón Merino Pérez; Jesús Merino Pérez.
Owner:Fibrostatin S.L.
Startup Companies
Name: Inhibitec-Anticuerpos S.L.
Date of Registration:05/03/2019
INPP5K controls the dynamic structure and signaling of wild-type and mutated, leukemia-associated IL-7 receptors
Moës B, Li H, Molina-Ortiz P, Radermecker C, Rosu A, Vande Catsyne CA, Sayyed SA, Fontela J, Duque M, Mostafa A, Azzi A, Barata JT, Merino R, Xu C, Desmet CJ, Schurmans S.
Blood. 2023 Apr 6;141(14):1708-1717.
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CD38 Deficiency Ameliorates Chronic Graft- Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism
Martínez-Blanco Á, Domínguez-Pantoja M, Botía-Sánchez M, Pérez-Cabrera S, Bello-Iglesias N, Carrillo-Rodríguez P, Martin-Morales N, Lario-Simón A, Pérez-Sánchez-Cañete MM, Montosa-Hidalgo L, Guerrero-Fernández S, Longobardo-Polanco VM, Redondo-Sánchez S,
Front Immunol. 2021 Aug 24;12:713697.
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Anti-IL17 treatment ameliorates Down syndrome phenotypes in mice.
N. Rueda, V. Vidal, S. García-Cerro, J.O. Narcís, M. Llorens-Martín, A. Corrales, S. Lantigua, M. Iglesias, J. Merino, R. Merino* and C. Martínez-Cué*.
Brain Behav. Immun.2018, 73:235-251. doi: 10.1016/j.bbi.2018.05.008.
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CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism.
S. García-Rodríguez, A. Rosal-Vela, D. Botta, L.M. Cumba-García, E. Zumaquero, V. Prados-Maniviesa, D. Cerezo-Wallis, N. Lo Buono, J.A. Robles-Guirado, S. Guerrero, E. González-Paredes, E. Andrés-León, A. Corbí, M. Mack, F. Koch-Nolte, R. Merino, M. Zubia
Sci. Rep. 2018, 8:3357. doi: 10.1038/s41598-018-21337-6.
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Map3k8 modulates monocyte state and atherogenesis in ApoE-/- mice.
C. Sanz Garcia, A. Sanchez, C. Contreras Jurado, C. Cales, C. Barranquero, M. Muñoz, R. Merino, P. Escudero, M.J. Sanz, J. Osada, A. Aranda and S. Alemany.
Arterioscler. Thromb. Vasc. Biol. 2017, 37:237-246.
doi: 10.1161/ATVBAHA.116.308528.
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CD6 modulates the threshold for thymocyte selection and peripheral T cell homeostasis.
M. Orta-Mascaró, M. Consuegra-Fernández, E. Carreras, R. Roncagalli, A. Carreras-Sureda, P. Alvarez, L. Girard, I. Simões, M. Martínez-Florensa, F. Aranda, R. Merino, V. G. Martínez, R. Vicente, J. Merino, A. Sarukhan, M. Malissen, B. Malissen and F. Loza
J. Exp. Med. 2016, 213: 1387-1397. doi: 10.1084/jem.20151785.
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Bone morphogenetic protein and activin membrane-bound inhibitor, a transforming growth factor β rheostat that controls murine Treg cell/Th17 cell differentiation and the development of autoimmune arthritis by reducing interleukin-2 signaling.
J. Postigo, M. Iglesias, P. Álvarez, J.J. Augustin, L. Buelta, J. Merino and R. Merino.
Arthritis Rheumatol. 2016, 68:1551-1562.doi: 10.1002/art.39557.
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Supporting data for the MS identification of distinct transferrin glycopeptide glycoforms and citrullinated peptides associated with inflammation or autoimmunity.
A. Rosal-Vela, A. Barroso, E. Giménez, S. García-Rodriguez, V. Longobardo, J. Postigo, M. Iglesias, A. Lario, J. Merino, R. Merino, M. Zubiaur, V. Sanz-Nebot and J. Sancho.
Data in Brief 2016, 6: 587-602.
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Identification of multiple transferrin species in spleen and serum from mice with collagen-induced arthritis which may reflect changes in transferrin glycosylation associated with disease activity: The role of CD38.
A. Rosal-Vela, A. Barroso, E. Giménez, S. García-Rodriguez, V. Longobardo, J. Postigo, M. Iglesias, A. Lario, J. Merino, R. Merino, M. Zubiaur, V. Sanz-Nebot, and J. Sancho.
J.Proteomics 2016, 134: 127–137. doi: 10.1016/j.jprot.2015.11.023.
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Distinct serum proteome profiles associated with collagen-induced arthritis, and Complete Freund’s Adjuvant-induced inflammation in CD38-/- mice: the discriminative power of protein species or proteoforms.
A. Rosal-Vela, S. García-Rodríguez, J. Postigo, M. Iglesias, J. Merino, R. Merino, M. Zubiaur and J. Sancho.
Proteomics, 2015, 15: 3382-3393 doi: 10.1002/pmic.201400536.
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Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.
R. Fenutrıa, VG. Martinez, I. Simoẽs, J. Postigo, V. Gil, M. Martínez-Florensa, J. Sintes, R. Naves, KS. Cashman, J. Alberola-Ila, M. Ramos-Casals, G. Soldevila, C. Raman, J. Merino, R. Merino, P. Engel and F. Lozano.
PLoS ONE, 2014, 9: e84895. DOI: 10.1371/journal.pone.0084895.
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The Glucocorticoid-Induced TNFR-Related protein (GITR) contributes to the systemic adjuvanticity of the Escherichia coli heat-labile enterotoxin.
E. Tamayo, J. Postigo, J. González, M. Fernández-Rey, M. Iglesias, I. Santiuste, C. Riccardi, R. Rappuoli, G. del Giudice, R. Merino* and J. Merino*.
Eur. J. Immunol. 2010, 40: 754-763.
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B-cell overexpression of Bcl-2 cooperates with p21 deficiency for the induction of autoimmunity and lymphomas.
I. Santiuste, L. Buelta, M. Iglesias, F. Genre, F. Mazorra, S. Izui, J. Merino and R. Merino.
J. Autoimmun. 2010, 35, 316-324.
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BMP and Activin membrane-bound inhibitor (BAMBI) reveals the involvement of the TGF-β family in pain modulation.
M. Tramullas, A. Lantero, A. Díaz, N. Morchón, D. Merino, A. Villar, D. Buscher, R. Merino, J.M. Hurlé, J.C. Izpisúa-Belmonte, M.A. Hurlé.
J. Neurosci. 2010, 30, 1502-1511.
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Leflunomide derivative FK778 inhibits production of antibodies in an experimental model of alloreactive T-B cell interaction.
MªA. Ramos-Barrón, C. Gómez-Alamillo, I. Santiuste, C. Agüeros, L. San Cosme, A. Benito, T. Gimenez, J. Merino, R Merino and M Arias. Exp. Clin. Trasplant. 2009, 4: 218-224.
Exp. Clin. Trasplant. 2009, 4: 218-224.
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Gender differences of echocardiographic and gene expression patterns in human pressure overload left ventricular hypertrophy.
A.V. Villar, M. Llano, M. Cobo, V. Expósito, R. Merino, R. Martín-Durán, M.A. Hurlé, and J.F. Nistal. J. Mol. Cell. Card. 2009, 46: 526-535.
J. Mol. Cell. Card. 2009, 46: 526-535.
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Involvement of the intrinsic and extrinsic cell death pathways in the induction of apoptosis of mature lymphocytes by the Escherichia coli heat-labile enterotoxin.
E. Tamayo, J. Postigo, G. del Giudice, R. Rappuoli, A. Benito, H. Yagita, R. Merino* and J. Merino* Eur. J. Immunol. 2009, 39: 439-446.
Eur. J. Immunol.2009, 39: 439-446.
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