Redox Biology and Metabolism in Cancer

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Rosa M. Sáinz obtained her PhD at the Universidad de Oviedo. She was a postdoctoral fellow at the Instituto Universitario de Oncología de Asturias (IUOPA) from 2000 to 2001, before receiving a grant from the Fulbright-MEC programme to complete a postdoctoral fellowship at the Health Science Center in San Antonio (TX, US) between 2001 and 2004. She returned to the Universidad de Oviedo in 2005, where she worked as a Ramón y Cajal researcher until 2009 and she has been a Tenured Lecturer in Cell Biology since 2010.

Since then, Dr Sainz’s research has focused on the role of redox metabolism in cell survival and the signalling mechanisms involved in this process, as well as the acquisition of resistance phenotypes, and cell-differentiation mechanisms in tumour cells. These lines of research have been funded by public research bodies at the regional (Asturian Regional Research Plan), national (Instituto de Salud Carlos III Health Research Fund, Ministry of Economic Affairs and Digital Transformation) and international (JPI ERA-HDHL ).

She has authored over 90 publications in scientific journals, with over 10,000 cumulative citations, has a h-index of 42 and is one of the leading Spanish scientific authors in the field of Endocrinology and Metabolism. She is currently the academic secretary of IUOPA and is on the board of directors of the Sociedad Española de Biología Celular (Spanish Society of Cell Biology).

Laboratorio 8.11, Depto Morfología y Biología Celular

Facultad de Medicina

Julián Clavería, 6 33006 Oviedo, Spain.

E-mail: sainzrosa@uniovi.es

Twitter: @bioxgroup

Website

Name	Organisation	Activity	Euraxess classification
Alcón Rodríguez, Sergio	FINBA	Research	R1
Álvarez Artime, Alejandro	Universidad de Oviedo	Research	R1
Artime Naveda, Francisco	Universidad de Oviedo	Research	R1
Cernuda Cernuda, Rafael	Universidad de Oviedo	Research/Teaching	R3
García Alonso, José Ignacio	Universidad de Oviedo	Research/Teaching	R3
Hevia Sánchez, David	Universidad de Oviedo	Research/Teaching	R2
Mayo Barrallo, Juan Carlos	Universidad de Oviedo	Research/Teaching	R3
Morán Álvarez, Alba	Universidad de Oviedo	Research	R1
Quirós González, Isabel	Universidad de Oviedo	Research/Teaching	R2
Rodas Sánchez, Laura Covadonga	Universidad de Oviedo	Research	R1
Rodríguez González, Pablo	Universidad de Oviedo	Research/Teaching	R3
Sainz Menéndez, Rosa María	Universidad de Oviedo	Research/Teaching	R4

The main interest of the ‘Redox Biology and Metabolism in Cancer’ research group is exploring the role of reactive oxygen species as physiological agents in cell signalling mechanisms within biological processes.

1 - Redox Signalling in Processes of Cell Differentiation and Cell Death

The physiological levels of reactive oxygen and nitrogen species form part of a complex system of basic intracellular signalling which, by modifying cysteine residues from a wide range of proteins, participates in an intricate signalling system that regulates the activity of proteins such as kinases, proteases and transcription factors, which control the most essential cellular mechanisms.

The specific objectives of this line of research are to:

Determine how the proteins involved in redox homeostasis participate in cell survival mechanisms.
Evaluate the extent to which neuroendocrine differentiation mechanisms can act as a stress-response strategy which makes the tumour cells resistant to therapy.
Identify the role of H₂O₂ as a cell signaller in the cell-differentiation mechanisms of stem cells belonging to the spermatogenic series, and its involvement in fertility-related problems.

2 - Redox Control of Tumour Progression

Metabolic alterations of tumour cells, the infiltration of tumours by inflammatory cells and oncological treatments can all contribute to raising the levels of oxidative stress. The toxic effects of oxidative stress on normal cells can be avoided by boosting antioxidant defence mechanisms. However, such an increase within tumour cells strengthens the mechanisms of tumour progression and invasion, and prevents cell death. Our specific objectives in this line of research are as follows:

Describe the role of mitochondria and mitochondrial antioxidant proteins in tumour progression.
Determine the role of the TXNIP protein (TRX-interacting protein) as a bridge between glycolytic metabolism and redox balance in cancer.
Seek new biomarkers based on the redox changes that take place in tumour cells.

3 - The Participation of Circadian Redox Oscillations in Pathological Processes

Night work has been defined as a possible carcinogen. Our research group has spent over 20 years working on the biological properties of the pineal neuroindole melatonin which, as well as mediating the cycles of light and darkness, is a powerful endogenous antioxidant. Our specific objectives in this line of research are to:

Demonstrate the importance of melatonin throughout evolution as a modulator of the basic mechanisms of cell survival.
Investigate whether there is any redox control of the genetic machinery that regulates the circadian rhythm.
Determine the role of selenoproteins which participate in redox control and undergo non-transcriptional circadian changes in cancer.

4 - The Development of Analytical Methods Based on Isotope Dilution Analysis for the Absolute Quantification of Biomarkers in Cancer

The use of certain biomarkers has been seriously called into question in recent years. Some are non-specific markers, and as such have certain limitations. In other cases, biomarker levels may be affected by several factors that are not necessarily related to tumour growth. The specific objectives of our group in this line of research are to develop:

Exact and precise analytical methods for the determination of proteins and their subsequent utility as biomarkers.
Non-invasive methods for the determination of metabolic parameters that enable us to predict the probability of cancer recurrence.

Alvarez-Artime A, Cernuda-Cernuda R, Artime-Naveda F, Cepas V, Gonzalez-Menendez P, Fernandez-Vega S, Quiros-Gonzalez I, Sainz RM, Mayo JC. Melatonin-induced cytoskeleton reorganization leads to inhibition of melanoma cancer cell proliferation. International Journal of Molecular Sciences, (2020) 21 (2) IF: 4.183 Q2
Cepas V, Collino M, Mayo JC, Sainz RM. Redox signaling and Advanced Glycation Endproducts (AGEs) in diet-related diseases. Antioxidants (2020) 9(2), 142. IF: 4.520
Bouzas-Ramos D, Cigales-Canga J, Mayo JC, Sainz RM, Ruiz-Encinar J, and Costa-Fernandez JM*. Carbon Quantum Dots codoped with nitrogen and Lanthanides for Multimodal Imaging. Advanced Functional Materials (2019), 29, 1903884. IF: 15.621, D1
Gonzalez-Menendez P, Hevia D, Alonso-Arias R, Alvarez-Artime A, Rodriguez-Garcia A, Kinet S, Gonzalez-Pola I, Taylor N, Mayo JC, Sainz RM (2018). GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress. Redox Biology. 17, pp.112-127. IF: 7.126 D1
Moro-García MA, Mayo JC, Sainz RM, Alonso-Arias R (2018). Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes. Frontiers Immunol. 9, pp.339. IF: 6.429
Mayo JC, Sainz RM, Gonzalez Menendez P, Cepas V, Tan DX, Reiter RJ (2017). Melatonin and sirtuins: A “not-so unexpected” relationship. Journal of Pineal Res. 62(2). IF: 11.613 D1
Gonzalez-Menendez P, Hevia D, Mayo JC, Sainz RM. (2017). The dark side of glucose transporters in prostate cancer: are they a new feature to characterize carcinomas? International Journal of Cancer. 142-12, pp.2414-2424. IF: 7.360
Mayo JC, Hevia, D, Quiros-Gonzalez I, Rodriguez-Garcia, A, Gonzalez-Menendez P, Cepas V, Gonzalez-Pola I, Sainz RM (2017). IGFBP3 and MAPK/ERK signaling mediates melatonin-induced antitumor activity in prostate cancer. Journal of Pineal Research. IF: 11.613. D1
Hevia D, Gonzalez-Menendez P, Fernandez-Fernandez M, Cueto S, Rodriguez-Gonzalez P, Garcia-Alonso JI, Mayo JC, Sainz RM (2017). Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A ¹³C Stable Isotope-Resolved Metabolomic Study. International Journal of Molecular Science. 18-8, pp.1620-1639. IF: 3.68 Q2
Rodriguez-Garcia A, Hevia D, Gonzalez-Menendez P, Coppo L, Lu J, Holmgren A, Sainz RM (2017). Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells. Redox Biology. 12, pp.634-647. IF: 7.126 D1
Miar A, Hevia D, Muñoz-Cimadevilla H, Astudillo A, Velasco J, Sainz RM, Mayo JC (2015). Manganese superoxide dismutase (SOD2/MnSOD)/catalase and SOD2/GPx1 ratios as biomarkers for tumor progression and metastasis in prostate, colon and lung cancer. Free Radical Biology & Medicine. 85, pp.45- 55. IF: 5.784
Hevia D, Gonzalez-Menendez P, Quiros-Gonzalez I, Miar A, Rodriguez-Garcia A, Tan DX, Reiter RJ, Mayo JC, Sainz RM (2015). Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer. Journal of Pineal Research. 58-2, pp.234-250. IF: 9.6 D1
Gonzalez-Menendez P, Hevia D, Rodriguez-Garcia A, Mayo JC, Sainz RM* (2014). Regulation of GLUT Transporters by Flavonoids in Androgen-Sensitive and -Insensitive Prostate Cancer Cells. 155-9, pp.3238-3250. IF: 4.503

Establishing the role of Thioredoxin Interacting Protein (TXNIP) as a bridge between diabetes and redox signaling in the inhibition of prostate cancer

PI	Rosa M. Sainz, Juan C. Mayo
Team	Rafael Cernuda Cernuda, Isabel Quirós-Gonzalez, David Hevia, Miguel Alvarez Múgica, Mario Dominguez Esteban
Funding body	MICIU-AEI
Reference No	PID2019-111418RB-I00
Date	1/9/2020 – 31/8/2023
Budget	€167,706

The relevance of hydrogen peroxide signalling and the “redoxisome” in the function of androgens in normal cells and cancer cells

PI	Rosa M. Sainz
Team	Juan Carlos Mayo Barrallo, Jose Manuel García Fernandez, Rafael Cernuda Cernuda, Manuel Rivas Del Fresno, David Hevia Sánchez.
Funding Body	MINECO
Reference No	MINECO-17-BFU2016-79139-R
Date	30/12/2016 – 31/12/2020
Budget	€133,100

SALIVAGES – Innovative technological approaches to the validation of salivary AGEs as novel biomarkers for risk factors in diet-related diseases

PI	Rosa M. Sainz
Team	Juan Carlos Mayo Barrallo, Vanesa Cepas López
Funding Body	ERA-HDHL_MINECO
Reference No	MINECO-17-PCIN-2016-164
Date	01/12/2016 – 31/12/2020
Budget	€148,000

The synthesis of isotopically-enriched compounds as disease biomarkers, for application in clinical analysis methods based on isotope dilution analysis and mass spectrometry

PI	Pablo Rodríguez González
Team	José Ignacio García Alonso
Funding Body	ISC-Science S.L.
Reference No	FUO-091-17
Date	01/03/2017 – 28/02/2018
Budget	€26,819

Peripheral endometriosis markers related to inflammation

PI	Isabel Quirós González
Funding Body	ISPA/FINBA
Date	01/01/2018 – 31/12/2018
Budget	€6000

Enriched stable isotopes

PI	José Ignacio García Alonso
Team	Rosa María Sainz Menéndez, Juan Carlos Mayo Barrallo, Pablo Rodríguez González, Rafael Cernuda Cernuda, David Hevia Sánchez, Isabel Quirós González, Vanesa Cepas López, Laura Covadonga Rodas Sánchez, Alejandro Álvarez Artime
Funding Body	Gobierno del Principado de Asturias
Reference No	IDI/2018/000239
Date	01/01/2018 – 31/12/2020
Budget	€141,900

Determination of the concentration and isotopic fractionation of mercury species in biological samples by coupling gas chromatographs with different mass spectrometers

PhD Student: Silvia Queipo Abad
Supervisor: José Ignacio García Alonso
Universidad de Oviedo – Faculty of Chemistry
July 2019

Development of analytical strategies for the quantification of biomolecules through liquid chromatography, isotope dilution and mass spectrometry

PhD Student: Amanda Suárez Fernández
Supervisors: José Ignacio García Alonso, Pablo Rodríguez González
Universidad de Oviedo – Faculty of Chemistry
December 2019

Regulation of facilitative glucose transporters (glut) during prostate tumour progression

PhD Student: Pedro González Menéndez
Supervisors: Rosa María Sainz Menéndez, Juan Carlos Mayo Barrallo, David Hevia Sánchez
Universidad de Oviedo – Faculty of Medicine. Instituto Universitario de Oncología del Principado de Asturias
April 2017
International Honours
Outstanding PhD Award

Changes in SOD2 levels during carcinogenesis in TRAMP mice: redox imbalance as a possible new biomarker for tumour progression and metastasis

PhD Student: Ana Belén Miar Cuervo
Supervisors: Rosa María Sainz Menéndez, Juan Carlos Mayo Barrallo
Universidad de Oviedo
February 2015
Summa cum laude
International Honours

Redox control of cell survival in prostate cancer

PhD Student: Aida Rodríguez García
Supervisors: Rosa María Sainz Menéndez, Juan Carlos Mayo Barrallo
Universidad de Oviedo
May 2015
Summa cum laude
International Honours
Outstanding PhD Award

The biological activity of berry extracts in cells, animals and human samples

Type: University-Company FUO-286-17
Company Providing Funding: BQC S.L.
Duration: 1/7/2017 – 31/1/2018
Lead Researcher: Juan Carlos Mayo Barrallo
Total Project Cost: €12,610

Development of analytical methods for the new Bilastine synthesis pathway

Type: University-Company FUO-316-18
Company Providing Funding: Faes Pharma S.A.
Duration: 20/9/2018 – 31/4/2019
Lead Researcher: José Ignacio García Alonso
Total Project Cost: €20,859

BIOQUOCHEM S.L. (http://www.bioquochem.com/)
Date created: 14/05/2015
ISC-SCIENCE (Innovative Solutions in Chemistry, www.isc-science.com)
Date created: 16/05/2003

The use of melatonin in the treatment of neurodegenerative diseases

Inventors: C. Rodríguez, J.C. Mayo, R.M. Sáinz, H. Uría and I. Antolín
Application Number: P97012012
Priority Country: Spain
Priority Date: 1996
Owner: Universidad de Oviedo
Countries in which the patent applies: Spain

Anti-tumour activity in prostate cancer of the phenolic and polyphenolic compounds in cider

Inventors: Hevia D, Sainz RM, Mayo JC, Quiros I
Application Number: O-293-2008
Application Date: 26/06/2008
Application Date: 5/9/2008

Anti-tumour activity in prostate cancer of the phenolic and polyphenolic compounds in beer

Inventors: Hevia D, Sainz RM, Mayo JC, Quiros I
Application Number: O-294-2008
Application Date: 26/06/2008
Application Date: 5/9/2008

Method for the absolute quantification of peptides through tandem mass spectrometry, and its uses

Inventors: J.I. García Alonso, A. González Antuña and P. Rodríguez González
Application Number: P201400239
Priority Date: 21/03/2014
Owner: Universidad de Oviedo

European Researchers’ Night (27/9/2019)

Research Divisions