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Más allá de la huella metabólica: hacia la identificacion exhaustiva en metabolómica (TIDEMET)


Más allá de la huella metabólica: hacia la identificacion exhaustiva en metabolómica (TIDEMET)

Principal Investigator

Antonia García and Javier Rupérez (Co-IP)

Financial entity

Ministerio de Ciencia, Innovación y Universidades
Code: RTI2018-095166-B-I00


170,731 €


01/01/2019 – 31/12/2021

“MagMA” Applying Metabolomics to Unveil follow-up treatment biomarkers


Supervisor de Marie Curie: “MagMA” Applying Metabolomics to Unveil follow-up treatment biomarkers and Identify Novel Therapeutic Targets in Glioblastoma

Principal Investigator

Coral Barbas

Financial entity

MSCA-IF-2017 Project, Grant Agreement Number 799378   






Glioblastoma multiforme (GBM) is a malignant tumour originating from glial cells. It is the most common and devastating form of malignant brain tumour, containing self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumour initiation and therapeutic resistance. It leads to 225,000 deaths per year in the entire world. Standard treatment consists of maximal surgical resection, followed by radiotherapy with or without concomitant and adjuvant Temozolomide. Such treatment hardly increases patient survival and leads to a median overall survival of only 12–18 months.

By contrast, to other types of cancers, it appears uncertain that GBM incidence can be decreased by changing certain environmental factors, or anticipated from the presence of another disease or condition. Until date, all efforts that have been done to improve patient’s life have shown low efficacy and the survival of such patients has not improved much in the last 60 years. Therefore, it seems clear that new methods for diagnosis, prognosis and treatment are needed.

To better understand GBM tumour biology, several groups worldwide have turned to high dimensional profiling studies. On 2018 Verhaak and collaborators described several GBM phenotypes; Proneural, Neural, Classical and Mesenchymal, each with distinguishing hallmark mutations, copy number alterations, epigenetic alterations, and clinical features. Additionally, treatment efficacy differs per subtype. Nevertheless, a full metabolomic profile had not been performed until date.

The first objective of our study was to investigate the underlying metabolic differences between the most extreme phenotypes (Proneural and Mesenchymal). These generate a characteristic fingerprint, not yet reported until now, thereby providing a better understanding of glioma biology. This finding could help in the development of new strategies to fight the tumour and lead to more personalized therapy.

Another difficulty of GBM is that both, confirmation and follow up of the tumour process are restricted by anatomical location. Nevertheless, neural cells are able to release extracellular vesicles (EVs), which cross the blood-brain barrier and could be detected within the blood, offering a potential new way for detection and treatment monitoring. The second objective of the project was to study the metabolic profile of the EVs released by those subtypes. This research effort has helped to draw the EVs metabolome and to elucidate whether or not the metabolites are directly packaged into specific EVs and their possible function in the surrounding cells. Moreover, it gives the opportunity of finding a metabolite profile characteristic of tumour subtype that could be used as a biomarker.

Dissemniation activities

Conference talks

  • Application of metabolomics in the identification of new therapeutic targets in glioblastoma, as biomarkers for its treatment and evolution. Oral communication. CEU San Pablo Interuniversity Researchers Conference 31st January 2020 (D 6.2)
  • Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2. Poster presentation. International Conference of Extracellular Vesicles 2019 at Kyoto, Japan on 24th-28th April. https://www.isev.org/page/ISEV2019

Public engagement activities

Outreach activities

Newspaper Interviews

University website News

Other activities

Teaching activities

  • Dr Melero has contributed to teaching activities participating at Genetics grade in 2018-2019 and 2019-2020 academic years teaching the subject “Instrumental techniques”, and “Instrumental and Bioanalytical techniques” at bilingual grade of Biotechnology at 2018-2019 academic year, with a total of 60h.

Supervision of students

  • The researcher has supervised Bethany Pembridge, a one year Erasmus student to conduct her own research project at “Universidad CEU-San Pablo”.



Química Analítica Avanzada para Ciencias de la Vida. ACCLifeSci. ERASMUS+


Química Analítica Avanzada para Ciencias de la Vida. ACCLifeSci. ERASMUS+

Principal Investigator

Antonia García

Financial entity

Unión Europea. Agencia ERASMUS +


298,631 €


01/09/2015 – 31/08/2018



The educational and scientific project: Advanced Analytical Chemistry for Life Sciences (ACCLifeSci), coordinated by Prof. Dr Hab. Elżbieta Skrzydlewska, the Dean of MUB’s Faculty of Pharmacy, and financed from Erasmus+ Programme joins three universities:

  • Medical University of Białystok, Faculty of Pharmacy with the Division of Laboratory Medicine (The Leader)
  • Aveiro University (Portugal, partner)
  • University San Pablo-CEU (Spain, partner)

The Intellectual Outputs

Manuscript for teaching AAC in omics sciences:

E-materials for teaching AAC in omics sciences:

Terms of use: All the above Intellectual Outputs are licensed under Creative Commons Attribution-NonCommercial 3.0 License CC BY-NC 3.0. They are attributed to Pedro Domingues, Antonia García and Elżbieta Skrzydlewska (editors) and the original versions can be found under the links above.

The Intellectual Outputs were created in Białystok (Poland), Aveiro (Portugal) and Madrid (Spain) in 2015-18, completed in August 2018.



Metabolomics can be considered a well stablished discipline for studying the ultimate expression of the phenotype. Nevertheless, this complete characterization has not been achieved yet. In a typical untargeted metabolomics study, more than 50% of the signals that can be assigned to a unique molecular entity remain unidentified.
As the overall objective of the project, we expect to cover part of this gap, and to increase the number of identified metabolites, by improving in specific points of the methodology. Furthermore, with such improvement in metabolite identification, we aim at achieving better understanding of the metabolic processes involved. We propose to achieve this goal by means of 6 specific objectives:

  1. Expanding identification capabilities by GC-MS
    • The comprehensive characterization of biological samples with authentic standards and reference materials, as well as the low energy source in GC-QTOF-MS, will enlarge our metabolite libraries. Among those metabolites, those related to the gut microflora, that may involve a complex interplay and cross talk between the immune system, the endocrine system, and even the Central Nervous System, will be part of the non-previously identified compounds. Moreover, new methodologies for sample treatment, and for volatile compounds, , will permit us to build a more complete and more detailed database of compounds.
  2. Extending identification capabilities by CE-MS
    • The implementation of new methods for the analysis of neutral and anionic compounds, along with the in-source fragmentation strategy in CE-MS will permit us to add new records to the database of identified compounds. Among the metabolites that could be identified with CEMS, the possible epi-metabolites, i.e. identified compounds that could be associated to simple metabolic processes such as methylation and acetylation, will be integrated into the biological interpretation of the processes involved in the different biological questions.
  3. Extending identification capabilities by LC-QTOF-MS: thorough identification of modified lipids and oxidized phospholipids
    • Lipids are still poorly represented in the databases, and this lack of records is even higher when dealing with oxidised lipids. We plan to expand our knowledge of these compounds, by means of advanced analytical strategies for purification and structural elucidation, combined with the work with CEU Mass Mediator (Objective 5)
  4. Extending identification capabilities by LC-QqQ-MS: Chiral Metabolomics
    • In addition, the differentiation of chiral compounds by means of advanced analytical strategies will expand the number of processes that could be elucidated. Different strategies: labelling agent and separation conditions will be optimized to stablish the definite chiral metabolomics method to be applied in CEMBIO.
  5. Development of the tool CEU Mass Mediator
    • We have worked extensively in the CEU Mass Mediator, and we plan to keep on working on this tool, adding more capabilities such as the spectral quality evaluation. In addition, better ways for integration of data from different instrumental platforms (LC/MS, CE/MS, GC/MS) and omics (proteomics, transcriptomics, genomics) will be studied.
  6. Applications
    • In the previous years, CEMBIO has been able to stablish a broad network of collaborators: Cardiovascular diseases, Obesity and bariatric surgery, Diabetes, Cancer, Perinatal metabolomics, Infectious diseases, and Neurodegenerative disorders