RESEARCH INTEREST
Chronic respiratory diseases represent one of the major global health burdens, affecting millions of people and placing a significant strain on healthcare systems. Among these, chronic obstructive pulmonary disease (COPD) stands out as a leading cause of reduced quality of life and premature mortality in patients who develop a vascular phenotype. This specific subgroup of patients with a vascular phenotype presents distinct prognostic and therapeutic implications, with a poor response to oxygen therapy and resistance to conventional treatments used for pulmonary hypertension of other etiologies. However, fundamental aspects such as its prevalence, natural history, and underlying molecular mechanisms remain insufficiently characterized.
In this context, our research aims to elucidate the molecular mechanisms responsible for vascular deterioration in chronic respiratory diseases associated with hypoxia. Our group has made pioneering contributions in this field by demonstrating that exposure to tobacco smoke can directly induce pulmonary vascular damage and by identifying key molecular mechanisms underlying COPD-associated pulmonary hypertension (Andreu-Martínez et al., 2025; Rodríguez-Pérez et al., 2025; Sevilla-Montero et al., 2022; Sevilla-Montero et al., 2021; Labrousse-Arias et al., 2017). Understanding the synergistic interaction between tobacco smoke and hypoxia—conditions that commonly coexist in clinical COPD—is essential for advancing pathophysiological knowledge and promoting the development of specific therapeutic interventions targeting this high-risk patient subgroup.
Thrombospondin-1 and pulmonary arterial hypertension: TSP1 role in artery muscularization and right ventricle hypertrophy. Proyectos de Cooperación Interuniversitaria UAM – Banco Santander con Estados Unidos. 2017-2019.
Estudio de nuevas dianas terapéuticas en la hipertensión pulmonar. Contribución del nexo TSP1/CD47 en las propiedades estructurales y funcionales de la arteria pulmonar en modelos de ratón. PI13/01866. ISCIII. 2014-2016.
Estudiar los mecanismos mediante los cuales, la hipoxia, a través de la regulación del nexo TSP1/CD47, induce cascadas de señalización que promueven la proliferación, migración y diferenciación de las células que componen la pared arterial pulmonar, afectando a su capacidad contráctil y de transporte.
Esta ayuda está financiada por el Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 y el ISCIII – Subdirección General de Evaluación y Fomento de la Investigación – y cofinanciadas por el FEDER, Programa Operativo de Economía Basada en el Conocimiento (2007‐2013) de acuerdo con el Reglamento (CE) nº 1083/2006 del Consejo de 11 de julio de 2006.
TSP1-CD47 in Promotion of PAH-Associated Vasoconstriction and Vascular Overgrowth. PA10-067. NIH. 2011-2015.
Bauer PM, Bauer EM, Rogers NM, Yao M, Feijoo-Cuaresma M, Pilewski JM, Champion HC, Zuckerbraun BS, Calzada MJ, Isenberg JS. Activated CD47 promotes pulmonary arterial hypertension through targeting caveolin-1. Cardiovasc Res 2012. 93: 682-693. FI: 5,940(Q1). PMID: 22215724. DOI: 10.1093/cvr/cvr356.
Fernández-Sánchez R, Berzal S, Sánchez-Niño MD, Neria F, Gonçalves S, Calabia O, Tejedor A, Calzada MJ, Caramelo C, Deudero JJ, Ortiz A. AG490 promotes HIF-1a accumulation by inhibiting its hydroxylation. Curr. Med. Chem. 2012. 19: 4014-4023. FI: 4,070(Q1). PMID: 22709000.
Fernández-Barral A, Orgaz JL, Gomez V, del Peso L, Calzada MJ, Jiménez B. Hypoxia Negatively Regulates Antimetastatic PEDF in Melanoma Cells by a Hypoxia Inducible Factor-Independent, Autophagy Dependent Mechanism. PLoS One 2012. . FI: 3,730(Q1). PMID: 22457728. DOI: 10.1371/journal.pone.0032989.
Bienes-Martinez, Raquel, Ordonez, Angel, Feijoo-Cuaresma, Monica, Corral-Escariz, Maria, Mateo, Gloria, Stenina, Olga, Jimenez, Benilde, Calzada, Maria J. Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via HIF-independent suppression of thrombospondin-1. Sci Rep 2012. 2: 788-0. FI: 2,927(Q1). PMID: 23145312. DOI: 10.1038/srep00788.
