Seve-Ballesteros Foundation Brain Tumour Group

Vacant Director

Graduate Students

María del Mar Gardeazabal

A decade of studies has underlined the complexity of the genetic events that characterise the genomic landscapes of common forms of human cancer, including gliomas. While a few cancer genes are mutated at high frequencies (>20%), the greatest number of cancer genes in most patients appear at intermediate frequencies (2–20%) or lower. Strikingly, the functional significance of the vast majority of these alterations remains elusive. A current high priority in glioma research is to functionally validate candidate genetic alterations in order to identify those that are significant for cancer progression and treatment response

In our laboratory, we use a combination of genomic analyses, mouse models, and primary tumour cell cultures, with the main goal of identifying the molecular mechanisms that could provide the basis for novel treatments for glioma patients.

Publications

Campisi L, Chizari S, Ho JSY, Gromova A, Arnold FJ, Mosca L, Mei X, Fstkchyan Y, Torre D, Beharry C, Garcia-Forn M, Jiménez-Alcázar M, Korobeynikov VA, Prazich J, Fayad ZA, Seldin MM, De Rubeis S, Bennett CL, Ostrow LW, Lunetta C, Squatrito M, Byun M, Shneider NA, Jiang N, La Spada AR, Marazzi I (2022). Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4. Nature 609, 945-952. CNIO Publication.
Laspidea V, Puigdelloses M, Labiano S, Marrodán L, Garcia-Moure M, Zalacain M, Gonzalez-Huarriz M, Martínez-Vélez N, Ausejo-Mauleon I, de la Nava D, Herrador-Cañete G, Marco-Sanz J, Guruceaga E, de Andrea CE, Villalba M, Becher O, Squatrito M, Matía V, Gállego Pérez-Larraya J, Patiño-García A, Gupta S, Gomez-Manzano C, Fueyo J, Alonso MM (2022). Exploiting 4-1BB immune checkpoint to enhance the efficacy of oncolytic virotherapy for diffuse intrinsic pontine gliomas. JCI Insight 7, e154812. CNIO Publication.
Schmitt MJ, Company C, Dramaretska Y, Barozzi I, Göhrig A, Kertalli S, Großmann M, Naumann H, Sanchez-Bailon MP, Hulsman D, Glass R, Squatrito M, Serresi M, Gargiulo G (2021). Phenotypic mapping of pathologic cross-talk between glioblastoma and innate immune cells by synthetic genetic tracing.. Cancer Discovery 11, 754-777. CNIO Publication.
Berg TJ, Marques C, Pantazopoulou V, Johansson E, von Stedingk K, Lindgren D, Jeannot P, Pietras EJ, Bergström T, Swartling FJ, Governa V, Bengzon J, Belting M, Axelson H, Squatrito M, Pietras A (2021). The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2. Cancer Res 81, 2101-2115. CNIO Publication.
Marques C, Unterkircher T, Kroon P, Oldrini B, Izzo A, Dramaretska Y, Ferrarese R, Kling E, Schnell O, Nelander S, Wagner EF, Bakiri L, Gargiulo G, Carro MS, Squatrito M (2021). NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1. Elife 10, e64846. CNIO Publication.
Aldaz P, Auzmendi-Iriarte J, Durántez M, Lasheras-Otero I, Carrasco-Garcia E, Zelaya MV, Bragado L, Olías-Arjona A, Egaña L, Samprón N, Morilla I, Redondo-Muñoz M, Rico M, Squatrito M, Maria-Alonso M, Fernández-Irigoyen J, Santamaria E, Larráyoz IM, Wellbrock C, Matheu A, Arozarena I (2021). Identification of a Dexamethasone Mediated Radioprotection Mechanism Reveals New Therapeutic Vulnerabilities in Glioblastoma. Cancers 13, 361. CNIO Publication.
Jiménez-Alcázar M, Curiel-García Á, Nogales P, Perales-Patón J, Schuhmacher AJ, Galán-Ganga M, Zhu L, Lowe SW, Al-Shahrour F, Squatrito M. (2021). Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma. Mol Cancer Ther 20, 1029-1038. CNIO Publication.
Schmitt MJ, Company C, Dramaretska Y, Barozzi I, Göhrig A, Kertalli S, Großmann M, Naumann H, Sanchez-Bailon MP, Hulsman D, Glass R, Squatrito M, Serresi M, Gargiulo G (2020). Phenotypic mapping of pathological crosstalk between glioblastoma and innate immune cells by synthetic genetic tracing.. Cancer Discovery (in press). CNIO Publication.
Oldrini B, Vaquero-Siguero N, Mu Q, Kroon P, Zhang Y, Galán-Ganga M, Bao Z, Wang Z, Liu H, Sa JK, Zhao J, Kim H, Rodriguez-Perales S, Nam DH, Verhaak RGW, Rabadan R, Jiang T, Wang J, Squatrito M (2020). MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nat Commun 11, 3833. CNIO Publication. Open Access
Pattwell SS, Arora S, Cimino PJ, Ozawa T, Szulzewsky F, Hoellerbauer P, Bonifert T, Hoffstrom BG, Boiani NE, Bolouri H, Correnti CE, Oldrini B, Silber JR, Squatrito M, Paddison PJ, Holland EC (2020). A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways. Nat Commun 11, 2977. CNIO Publication. Open Access
Lindroth AM, Park YJ, Matía V, Squatrito M (2020). The Mechanistic GEMMs of Oncogenic Histones. Hum Mol Genet 29, R226-R235. CNIO Publication.
Pudelko L, Rouhi P, Sanjiv K, Gad H, Kalderén C, Höglund A, Squatrito M, Schuhmacher AJ, Edwards S, Hägerstrand D, Berglund UW, Helleday T, Bräutigam L. (2020). Correction: Glioblastoma and glioblastoma stem cells are dependent on functional MTH1.. Oncotarget 11, 827. CNIO Publication.
Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero L, Martínez-Ricarte F, Huber-Ruano I, Nuciforo P, Pedrosa L, Marques C, Braña I, Garralda E, Vieito M, Squatrito M, Pineda E, Graus F, Espejo C, Sahuquillo J, Tabernero J, Seoane J (2019). LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun 10, 2416. CNIO Publication. Open Access
Zhao N, Sebastiano V, Moshkina N, Mena N, Hultquist J, Jimenez-Morales D, Ma Y, Rialdi A, Albrecht R, Fenouil R, Sánchez-Aparicio MT, Ayllon J, Ravisankar S, Haddad B, Ho JSY, Low D, Jin J, Yurchenko V, Prinjha RK, Tarakhovsky A, Squatrito M, Pinto D, Allette K, Byun M, Smith ML, Sebra R, Guccione E, Tumpey T, Krogan N, Greenbaum B, van Bakel H, García-Sastre A, Marazzi I (2018). Influenza virus infection causes global RNAPII termination defects. Nat Struct Mol Biol 25, 885-893. CNIO Publication.
Oldrini B, Curiel-García Á, Marques C, Matia V, Uluçkan Ö, Graña-Castro O, Torres-Ruiz R, Rodriguez-Perales S, Huse JT, Squatrito M (2018). Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling. Nat Commun 9, 1466. CNIO Publication. Open Access
Bejarano L, Schuhmacher AJ, Méndez-Pertuz M, Megías M, Blanco-Aparicio C, Martínez S, Pastor J, Squatrito M, Blasco MA (2017). Inhibition of Trf1 telomere protein impairs tumor initiation and progression in glioblastoma multiform mouse models and patient-derived xenografts. Cancer Cell 32, 590-607. CNIO Publication.
Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho AC, Lyu S, Li P, Li Y, Barthel F, Cho HJ, Lin YH, Satani N, Martinez-Ledesma E, Zheng S, Chang E, Sauvé CG, Olar A, Lan ZD, Finocchiaro G, Phillips JJ, Berger MS, Gabrusiewicz KR, Wang G, Eskilsson E, Hu J, Mikkelsen T, DePinho RA, Muller F, Heimberger AB, Sulman EP, Nam DH, Verhaak RGW (2017). Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell 32, 42-56. CNIO Publication.
Oldrini B, Hsieh WY, Erdjument-Bromage H, Codega P, Carro MS, Curiel-García A, Campos C, Pourmaleki M, Grommes C, Vivanco I, Rohle D, Bielski CM, Taylor BS,Hollmann TJ, Rosenblum M, Tempst P, Blenis J, Squatrito M, Mellinghoff IK (2017). EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer. Nat Commun 8, 2035. CNIO Publication. Open Access
Bowman R, Wang Q, Carro A, Verhaak RGW, Squatrito M (2017). GlioVis data portal for visualization and analysis of brain tumor expression datasets. Neuro-Oncology 19, 139-141. CNIO Publication.
Pudelko L, Rouhi P, Sanjiv K, Gad H, Kalderén C, Höglund A, Squatrito M, Schuhmacher AJ, Edwards S, Hägerstrand D, Berglund UW, Helleday T, Bräutigam L (2017). Glioblastoma and glioblastoma stem cells are dependent on functional MTH1. Oncotarget 8, 84671-84684. CNIO Publication.