Centro Andaluz de Biología Molecular y Medicina Regenerativa
Mercedes Tomé

Immunoresponse and signaling crosstalk in glioblastoma chemoresistance

Email: mercedes.tome@cabimer.es
ORCID ID: 0000-0001-8682-1800

Information

My research interest is focused on understanding the molecular mechanisms driving neurological disorders. Since my doctoral studies I have developed research projects in the fields of neurodevelopment, brain pathology and neuroregeneration strategies, in national and European research institutions. These studies have contributed to the understanding of the onset of congenital hydrocephalus, have identified novel mesenchymal stem cells with transplantation potential for the regeneration of spinal cord injuries, and described the implication of Notch2 signaling pathway in the initiation of glioblastoma (GBM), the most aggressive type of brain cancer.

Since my return in 2018 through the Spanish National Research Council (CSIC), our goal is the identification of molecular mechanisms driving GBM progression and therapy resistance. Indeed, the standard therapy against GBM has a mostly palliative role, and does not prevent tumor recurrence in 95% of the cases. Therefore, it is essential to understand at the molecular level the mechanisms of adaptation of these cancer cells to identify vulnerabilities that could be translated into more efficient therapeutic targets. We are particularly focused on the crosstalk between growth regulatory signaling pathways such as Notch and FGF, and on their coordination with cellular processes (cell cycle, transcription, etc) and with the tumor microenvironment (astrocytes) to evade therapy-mediated cell death.

We have already shown the relevance of interfering with Notch receptor maturation to enhance tumor immunoresponse through a crosstalk mechanism with other signaling pathways including calcium/NFAT and NF-kB to block PD-1-mediated immunosuppression (Tomé et al., 2019 Cancer Res). We have also identified a molecular mechanism of crosstalk between Notch2 and FGFR1 signaling pathways promoting neural stem cell resistance to cytotoxic insults that could have implications in tumorigenesis (Tomé et al., 2019 Stem Cell Res). We are also characterising the communication between Notch2 and FGFR1 signaling pathways in GBM, and the molecular mechanisms by which they contribute to cellular homeostasis to evade therapy.

Previous positions:

  • Senior postdoctoral researcher at the University of Bordeaux/INSERM (France)
  • Senior postdoctoral researcher at the University of Basel (Switzerland)
  • Postdoctoral researcher at the University of Glasgow (UK)
  • Visiting scientist at Prof. Esteban M. Rodríguez Lab, Austral University of Chile (Chile)
  • PhD student at the University of Malaga, Dept. of Cell Biology (Spain)

Projects

Projects

  • Metabolic and transcriptional regulation during glioblastoma chemotherapy resistance. Ministry of Science (PID2021-124251OB-I00), Spain. PI: Raúl V. Durán. 2022-2025
  • Youth Guarantee project for Regional Government of Andalusia 2021. Regional Government of Andalusia (EI-GARJUV-AND21-0128), Spain. PI: Mercedes Tomé. 2022-2023
  • Nutritional imbalance and cell death induction in cancer therapy: fundamental and translational aspects of glutamoptosis. Ministry of Science (PGC2018-096244-B-I00), Spain. PI: Raúl V. Durán. 2019-2022
  • Member of the PAIDI research group BIO-356 Metabolismo y Señalización Celular (Plan Andaluz de Investigación, Desarrollo e Innovación-PAIDI). PI: Raúl V. Durán. 2020-present.
  • Role of proprotein convertases and protein maturation in invasion and metastasis. SIRIC-BRIO and Institute Bergonié, France. PI: Majid Khatib. 2016-2018
  • Development of molecular strategies for therapeutic interference of glioblastomas. Oncosuisse (KFP OCS-01613-12-2004), Switzerland. PIs: Bernhard Bettler, Adrian Merlo, Brian Hemmings. 2010-2012
  • Flavonoids protection against neurodegeneration. Epsom Medical Research Charity, UK. PI: Trevor Stone. 2008-2009
  • Olfactory stem cells for central nervous system repair. Medical Research Council strategic stem cell grant (JSR), UK. PI: Susan C. Barnett. 2005-2008
  • Role of the ependyma in the aetiology of congenital hydrocephalus with cerebral aqueductal stenosis. Study in animals and clinical cases in humans. Ministry of Health and Consume (FIS 01-0948), Spain. PI: José Manuel Fernández Fígares. 2001-2004
  • Vascular permeability in the genesis of hydrocephalus. Regional Government of Andalusia (104/2002), Spain. PI: Miguel Ángel Arráez Sánchez. 2003-2004
  • Role of the ependyma in the aetiopathology of hydrocephalus. Regional Government of Andalusia (140/2001), Spain. PI: Miguel Ángel Arráez Sánchez. 2002-2003
  • Member of the PAIDI research group BIO-217 Biología y fisiología cellular-UMA (Plan Andaluz de Investigación, Desarrollo e Innovación-PAIDI). PI: José Becerra Ratia. 1999-2005

Publications

Publications

  1. Zarzuela L, Durán RV, Tomé M* (2025). Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance. Molecular Oncology. *Corresponding author
  2. Morillo-Huesca M, López-Cepero IG, Conesa-Bakkali R, Tomé M, Watts C, Huertas P, Moreno-Bueno G, Durán RV, Martinez-Fabregas J (2025). Radiotherapy resistance driven by asparagine endopeptidase through ATR pathway modulation in breast cancer. Journal of Experimental & Clinical Cancer Research.
  3. García-Vilchez R, Añazco-Guenkova AM, López J, Dietmann S, Tomé M, Jimeno S, Azkargorta M, Elortza F, Bárcena L, Gonzalez-Lopez M, Aransay AM, Sánchez-Martín MA, Huertas P, Durán RV, Blanco S (2023). N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer. Oncogene.
  4. Goméz-Marín E, Posavec M, Zarzuela L, Bausrto-Cayuela L, Guerrero-Martínez JA, Arribas G, Ceballos-Chávez M, Rodríguez-Paredes M, Tomé M, Durán RV, Buschbeck M, Reyes JC (2022). The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate cancer signaling pathways. Nucleic Acids Research.
  5. Nicastro R, Gaillard H, Zarzuela L, Péli-Gulli MP, Fernández-García E, Tomé M, García-Rodríguez N, Durán RV, De Virgilio C, Wellinger RE (2022). Manganese is a physiologically relevant TORC1 activator in yeast and mammals. ELife.
  6. Bodineau C, Tomé M, Murdoch PS, Durán RV (2022). Glutamine, MTOR and autophagy: a multiconnection relationship. Autophagy.
  7. Bodineau C, Tomé M, Courtois S, Costa ASH, Sciacovelli M, Rousseau B, Richard E, Vache P, Parejo-Pérez C, Bessede E, Varon C, Soubeyran P, Frezza C, Murdoch PS, Villar VH, Durán RV (2021). Two metabolic parallel pathways connect glutamine and mTORC1 to control glutamoptosis. Nature Communications.
  8. Nguyen TL, Nokin E, Muzotte E, Rezvani HR, Priault M, Bouchecareilh M, Redonnet-Vernhet I, Calvo J, Uzan B, ML, Terés S, Tomé M, Bodineau C, Galmar O, Pasquet JM, Rousseau B, van Liempd S, Falcon-Perez JM, Richard Pflumio F, Fuentes P, Toribio ML, Khatib AM, Soubeyran P, Murdoch PS, Durán RV (2021). Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia. Molecular Oncology.
  9. Tomé M*, Pappalardo A, Soulet F, López JJ, Olaizola J, Yannick L, Dubreil M, Mouchard A, Fessart D, Delom F, Pitard V, Bechade D, Fonck M, Rosado JA, Ghiringhelli F, Déchanet-Merville J, Soubeyran I, Siegfried G, Evrard S, Khatib AM* (2019). Proprotein convertases inactivation in T cells inhibits PD-1 expression and creates a favorable immune microenvironment in colorectal tumors. Cancer Research. *Corresponding authors.
  10. Tomé M*, Tchorz J, Gassmann M, Bettler B* (2019). Constitutive activation of Notch2 signaling confers chemoresistance to neural stem cells via transactivation of FGF receptor-1. Stem Cell Research. *Corresponding authors.
  11. Nguyen TL, Nokin MJ, Egorov M, Tomé M, Bodineau C, Minder L, Di Primo C, Wdzieczak-Bakala J, Garcia-Alvarez MC, Bignon J, Thoison O, Delpech B, Surpateanu G, Frapart YM, Peyrot F, Abbas K, Terés S, Evrard S, Khatib AM, Soubeyran P, Iorga B, Duran RV, Collin P (2018). mTOR inhibition via displacement of phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells. Cancer Research.
  12. Giachino C, Barz M, Tchorz JS, Tomé M, Gassmann M, Bischofberger J, Bettler B, Taylor V (2014). GABA suppresses neurogenesis in the adult hippocampus through GABAB receptors. Development.
  13. Tchorz JS, Tomé M, Cloëtta D, Sivasankaran B, Grzmil M, Huber RM, Rutz-Schatzmann F, Kirchhoff F, Schaeren-Wiemers N, Gassmann M, Hemmings BA, Merlo A, Bettler B (2012). Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry. Cell Death and Disease.
  14. Tomé M, Riddell JS, Barnett SC (2009). Identification of non-epithelial multipotent cells in the embryonic olfactory mucosa. Stem Cells.

A complete list of publications can be obtained at: https://orcid.org/0000-0001-8682-1800