Rare Tumors

RESEARCH LINES

Our research interest is focused on exploring the impact of the tumoral microenvironment and cellular metabolism on the development and progression of cancer, with the purpose of discovering biomarkers and new therapeutic alternatives. Our interest is especially centered on rare tumors pathogenically associated with alterations in Krebs cycle genes, as well as on mechanisms of response to hipoxia. These encompasses different types of neuroendocrine tumors and renal cancer.

Using genetic and epigenetic methodologies, alongside cutting-edge technologies like machine learning, bioprinting, and cellular and animal models, we explore how pseudo-hypoxia, mitochondrial activity, and cellular adhesion mechanisms involving protocadherins contribute to tumor initiation and metastatic disease progression.

Our goal is to translate our understanding of cellular physiopathology into practical clinical applications. We develop three-dimensional cellular models and analyse both tumoral and non-tumoral human tissue samples to identify valuable markers that can improve the diagnosis and prognosis of cancer.

Additionally, we conduct preclinical evaluations of both established antitumoral drugs and new compounds derived from natural sources, with the aim of potentially advancing therapeutic options for cancer treatment.

BIOGRAPHY OF THE GROUP HEAD

Senior Researcher R3 of the National Health System since 2008 and Full Professor at the University since 2002 (currently on voluntary leave), she holds a Bachelor’s and Doctorate in Medicine and Surgery obtained from the University of Seville in 1986 and 1990, respectively. Following a five-year postdoctoral period at Harvard University (1991-1996), she worked in the Department of Medical Physiology and Biophysics at the University of Seville from 1996-2002. This was followed by a position as a Miguel Servet Researcher at the Hospital Universitario Virgen del Rocío from 1999 to 2002 and the Hospital Universitario Central de Asturias from 2002 to 2008.

Throughout her career, she has transitioned from fundamental research in cellular and molecular biology to translational biomedical research, contributing to unravelling mechanisms involved in pre-mRNA splicing and the role of oxygen and oxygen-free radicals in inflammation, cellular excitability, and cancer pathogenesis..

SELECTED PUBLICATIONS

• Tamara Cubiella, Lucía Celada, Jaime San-Juan-Guardado, Raúl Rodríguez-Aguilar, Álvaro Suarez-Priede, María Poch, Francisco Dominguez, Iván Fernández-Vega, Pedro Montero-Pavón, Mario F Fraga, Yoichiro Nakatani, So Takata, Shinichi Yachida, Nuria Valdés, María-Dolores Chiara. PCDHGC3 hypermethylation as a potential biomarker of intestinal neuroendocrine carcinomas. J Pathol. 2024.
• Celada L, Cubiella T, San-Juan-Guardado J, Gutiérrez G, Beiguela B, Rodriguez R, Poch M, Astudillo A, Grijalba A, Sánchez-Sobrino P, Tous M, Navarro E, Serrano T, Paja M, Valdés N, Chiara MD. Pseudohypoxia in paraganglioma and pheochromocytoma is associated with an immunosuppressive phenotype. J Pathol. 2023 Jan;259(1):103-114. doi: 10.1002/path.6026. Epub 2022 Dec 1. PMID: 36314599; PMCID: PMC10107524.
• Celada L, Cubiella T, San-Juan-Guardado J, San José Martínez A, Valdés N, Jiménez-Fonseca P, Díaz I, Enguita JM, Astudillo A, Álvarez-González E, Sierra LM, Chiara MD. Differential HIF2α Protein Expression in Human Carotid Body and Adrenal Medulla under Physiologic and Tumorigenic Conditions. Cancers (Basel). 2022 Jun 17;14(12):2986. doi: 10.3390/cancers14122986. PMID: 35740651; PMCID: PMC9221385.
• Sáenz-de-Santa-María I, Celada L, San José Martínez A, Cubiella T, Chiara MD. Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2. Cancers (Basel). 2020 Dec 10;12(12):3708. doi: 10.3390/cancers12123708. PMID: 33321813; PMCID: PMC7764466.
• Bernardo-Castiñeira C, Valdés N, Celada L, Martinez ASJ, Sáenz-de-Santa-María I, Bayón GF, Fernández AF, Sierra MI, Fraga MF, Astudillo A, Jiménez-Fonseca P, Rial JC, Hevia MÁ, Turienzo E, Bernardo C, Forga L, Tena I, Molina-Garrido MJ, Cacho L, Villabona C, Serrano T, Scola B, Chirivella I, Del Olmo M, Menéndez CL, Navarro E, Tous M, Vallejo A, Athimulam S, Bancos I, Suarez C, Chiara MD. Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5673-5692. doi: 10.1210/jc.2018-01471.PMID: 31216007.