RESEARCH INTEREST
Our research group is a well-established team with national and international recognition in the field of endocrinology, and a distinguished track record in the study of autoimmune thyroid diseases (AITDs). The group combines the extensive clinical expertise of Dr. Mónica Marazuela with the basic scientific perspective of Dr. Rebeca Martínez-Hernández.
The group’s main research focus is on autoimmune thyroid diseases (AITDs), such as Graves’ disease (GD). Within this line, the group is a pioneer in the study of thyroid eye disease (TED), also known as Graves’ orbitopathy, a secondary manifestation of GD. The primary objective of the group is to identify novel biomarkers and susceptibility pathways through the integration of multi-omics approaches. This big data–based strategy enables a deeper understanding of disease pathophysiology and the cellular microenvironment, facilitating the development of innovative and personalized therapies.
Between 2020 and 2025, the group has carried out 13 competitively funded projects from public and private sources, six of which have focused specifically on AITDs, including TED. Research in this area has gained particular momentum following the award of the 2023 Clinical Research Grant in General Endocrinology and Metabolism from the Spanish Society of Endocrinology and Nutrition (SEEN). This ongoing project involves professionals from eight hospitals organized into five geographical nodes, thereby expanding the group’s national and international collaborative network.
In this context, the group is supported by the Spanish Association of Patients with Thyroid Eye Disease (TEDSpain, https://tedspain.org), a non-profit organization established to improve diagnosis, treatment, and patient support, promote research, and raise awareness of TED in Spain. The involvement of TEDSpain strengthens connections with both patients and healthcare professionals, facilitates the identification of unmet clinical needs, and provides a valuable channel for the dissemination and translation of scientific results into improved clinical care and patient stratification. In parallel, active participation in the European Group on Graves’ Orbitopathy (EUGOGO) further enhances the group’s visibility and impact at the European level.
The group’s work has led to significant contributions in this field, including the characterization of alterations in regulatory T cells (Treg), Th17 lymphocytes, and NK cells (J Clin Endocrinol Metab., 2020; Endocrine, 2024), as well as in other endocrine disorders, such as the identification of Tr1 lymphocytes in patients with type 2 diabetes (J Endocrinol Invest., 2024).
In this area, the group maintains strong collaborations with the Departments of Immunology, Rheumatology, and Dermatology at Hospital Universitario de La Princesa, as well as with leading research centers such as the Spanish National Cancer Research Centre (CNIO) (Dr. Mercedes Robledo and Fátima Al Yashour), Dr. Pilar Santisteban (Instituto de Investigaciones Biomédicas Alberto Sols, IIBM), and Dr. Pablo Valderrabano (Hospital Ramón y Cajal). Through these collaborations, predictive biomarkers for AITDs have been identified (Journal of Autoimmunity, 2020), and miRNA and mRNA data have been integrated, highlighting the role of HDAC9 in immune regulation (J Clin Endocrinol Metab., 2021; Int J Mol Sci., 2023).
More recently, the group has characterized thyroid tissue samples from AITD patients using spatial transcriptomics, enabling the identification of: CD74/MIF+ thyrocytes involved in chronic inflammation; Damaged thyrocytes in Hashimoto’s thyroiditis; Inflammation-associated fibroblasts in Hashimoto’s thyroiditis; Myofibroblasts with adipogenic features (ADIRF+) and diaphragmed fenestrated capillaries (PLVAP+) in GD (Nature Communications, 2024; Biomed Pharmacother., 2026).
At the international level, the group maintains strong collaborations with leading researchers and institutions, including Philippe Bertolino and Gérald Raverot (Centre de Recherche en Cancérologie and École Normale Supérieure, Lyon, France), Franck Picard (École Normale Supérieure, Lyon, France), Roberto González Amaro (CICSaB, Universidad Autónoma de San Luis Potosí, Mexico), George J. Kahaly (Johannes Gutenberg University, Mainz, Germany), and Mario Salvi (Graves Orbitopathy Center, Milan, Italy).
The group has further strengthened its international collaborations in AITDs through its integration into EUGOGO and the Research Observership Program of the European Society of Endocrinology (ESE-EYES). In addition to advancing basic knowledge of AITDs and thyroid eye disease, the group has a strong translational component, participating in clinical trials with innovative therapies in collaboration with the pharmaceutical industry, demonstrating its capacity for knowledge transfer and patentable developments. These collaborations encompass basic and translational research, methodological validation, sample analysis, and PhD training.
The group also develops a second research line focused on the identification of biomarkers for the diagnosis and aggressiveness of neuroendocrine tumors, particularly those related to proliferation and metastatic potential. In this area, the group is part of the Spanish Network for Rare Diseases (CIBERER), forming group GC14/ER/12, and leads the Spanish Molecular Registry of Pituitary Adenomas (REMAH), which includes 1,400 registered patients.
This strategy enables comparative analyses between molecular profiles of different adenoma types and patient clinical phenotypes, promoting a deeper understanding of disease and facilitating personalized treatment selection. In this line, the group has received funding for a personalized medicine project within the PMP-ISCIII program (ACROMICS PMP22/000021), in collaboration with Dr. Manel Puig (Trias i Pujol Institute).
This collaborative approach has advanced the understanding of the molecular landscape of GH-secreting tumors and fostered the development of innovative tools to improve diagnosis and treatment in acromegaly. Recently, the clinical-pathological spectrum of GH- and PRL-producing tumors in acromegaly has been characterized, providing new insights into their biological heterogeneity and clinical relevance (J Clin Endocrinol Metab., 2025).
Furthermore, the group has identified a novel diagnostic marker predicting aggressive behavior in pituitary neuroendocrine tumors, published in Modern Pathology (2024). This discovery led to the institutional registration of a diagnostic method as a European patent (EP22382079; PCT/EP2023/052006), reinforcing the translational impact of the research.
Since 2022, a third comprehensive research line has been established in the field of diabetes, addressing both basic and translational aspects. This project is led from our center in collaboration with Hospital Universitario Basurto (Bilbao) and Hospital Universitario Severo Ochoa (Leganés), and examines clinical, technological, and molecular factors to better understand the impact of the disease.
This work has resulted in numerous scientific publications across high-impact journals (list retained as in original). This integrative approach aims to optimize therapeutic strategies tailored to individual patient characteristics, promoting more effective and equitable diabetes management.
Currently, the group is also participating in two clinical trials in the field of diabetes.
Integromics in Autoimmune Thyroid Diseases: Combining miRNome, transcriptome and single cell analysis to characterize new clinical approaches and susceptibility pathways in AITD. PI19/00584. ISCIII. 2020-2022.
Investigar el papel del cilio primario del tirocito y su relación con los linfocitos infiltrantes en ETAI. Proporcionar asociaciones novedosas entre el microambiente inmune y los tironcitos en ETAI mediante secuenciación masiva de una sola celula.
Esta ayuda está financiada por el Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 y el ISCIII – Subdirección General de Evaluación y Fomento de la Investigación – y cofinanciadas por el Fondo Europeo de Desarrollo Regional, Programa Operativo Plurirregional de España 2014-2020 (Objetivo temático “Potenciar la investigación, el desarrollo tecnológico y la innovación”; Objetivo Específico “Fomento y generación de conocimiento de frontera y de conocimiento orientado a los retos de la sociedad, desarrollo de tecnologías emergentes”; Actuación “Proyectos de investigación orientados al Reto de Salud, Cambio Demográfico y Bienestar”, y se regirán de acuerdo con el Reglamento (UE) Nº 1303/2013 y de acuerdo al Reglamento (UE) Nº 1301/2013 del Parlamento Europeo y del Consejo, de 17 de diciembre de 2013 sobre Fondo Europeo de Desarrollo Regional.
Estudio del microambiente celular en tumores neuroendocrinos gastroenteropancreáticos. Caracterización de la respuesta inmunológica peritumoral y relación con el marcador de hipoxia/estrés tisular lat-1. Grupo Español de Tumores Neuroendocrinos (GETNE). 2017-2019.
Estudio de integración de miRNAS y mRNAS en las enfermedades tiroideas autoinmunes: análisis de vías de susceptibilidad y marcadores de la enfermedad. PI16/02091. ISCIII. 2017-2019.
Estudio integrativo de miRNAs y mRNAs secuenciados a partir de biopsias de tiroides de pacientes con ETAI y de controles.
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 Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014-2020 de acuerdo al Reglamento (UE) Nº 1303/2013.
Identificación y caracterización de microrRNAs implicados en la etiopatogenia de las enfermedades tiroideas autoinmunes. PI13/01414. ISCIII. 2014-2016.
Esta ayuda está financiada por el Plan Estatal I+D+i y al ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, cofinanciada 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, por el que se establecen las disposiciones generales relativas al Fondo Europeo de Desarrollo Regional, al Fondo Social Europeo y al Fondo de Cohesión.
Immunoregulatory molecules and biomarkers predicting response to biological therapies and disease severity in immune-medi-ated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041.Coordinador. 2014-2016.
Esta ayuda está financiada por el Plan Estatal I+D+i y al ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, cofinanciada 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, por el que se establecen las disposiciones generales relativas al Fondo Europeo de Desarrollo Regional, al Fondo Social Europeo y al Fondo de Cohesión.
Sacristán P, Serrano-Somavilla A, González-Amaro R, Martínez-Hernández R, Marazuela M. Analysis of expression of different histone deacetylases in autoimmune thyroid disease. J Clin Endocrinol Metab. 2021 Jul 7:dgab526. PMID: 34272941. DOI: 10.1210/clinem/dgab526.
Puig M, Bernabeu I, Pico A, Biagetti B, Gil J, Alvarez C, Jorda M, Marques M, Soldevila B, Galvez M, Camara R, Aller J, Lamas C, Marazuela M. Pasireotide in the Personalized Treatment of Acromegaly. Front Endocrinol (Lausanne). 2021. 648411-648411. IF: 5, 555(Q1). PMID: 33796079. DOI: 10.3389/fendo.2021.648411.
Ortega AC, Martínez R, Monsiváis A, Serrano A, Sánchez R, González R, Marazuela M. Quantitative and Functional Analysis of PD-1+ NK Cells in Patients With Autoimmune Thyroid Disease. J Clin Endocrinol Metab. 2020. 105. (11):dgaa569. IF: 5, 958. (Q1). PMID: 32823277. DOI: 10.1210/clinem/dgaa569.
Sampedro M, Bouthelier A, Serrano A, Martinez R, Adrados M, Martin E, Munoz de Nova JL, Cameselle JM, Blanco C, Cabezas JM, Diaz JA, Garcia R, Aragones J, Marazuela M. LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel). 2020. 12. (10):2968. IF: 6, 639. (Q1). PMID: 33066332. DOI: 10.3390/cancers12102968.
Martínez R, Serrano A, Ramos A, Sampedro M, Lens A, Muñoz De Nova JL, Triviño JC, González MU, Torné L, Casares J, Martín NB, Sánchez F, Marazuela M. Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases. EBioMedicine. 2019. 50. 329-342. IF: 5, 736. (Q1). PMID: 31735554. DOI: 10.1016/j.ebiom.2019.10.061.
