Grupo de Tumores Cerebrales Fundación Seve-Ballesteros

Massimo Squatrito Jefe de Grupo
T +34 (+34) 917 328 000 (Ext 3850)
msquatrito@cnio.es

Investigadores

Bárbara Oldrini

Becarios Post-doctorales

Miguel Jiménez

Becarios Pre-Doctorales

María del Mar Gardeazabal
Verónica Matía

Técnicos de Laboratorio

Alicia Marie Gaëlle Leblond

Glioblastoma (GBM) is the most common and lethal primary central nervous system tumour in adults. Despite the recent advances in treatment modalities, GBM patients generally respond poorly to all therapeutic approaches and prognosis remains dismal. Radiation and chemo-resistance are characteristic of various cancer types, however it is not clear if this therapy resistance is a consequence of tumour progression or if it is intrinsically associated with the genetic events that lead to the tumour formation in the first place. Gaining insights into the pathways that determine this poor treatment response will be instrumental for the development of new therapeutic modalities.

In our laboratory, we use a variety of approaches − both genetic and small molecule drug screenings − coupled with in vivo GBM mouse models in order to identify genes involved in therapy resistance of gliomas. We reason that these studies will help to define new therapeutic targets for treatment of brain tumours.

Publicaciones

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. Publicación CNIO.
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. Publicación CNIO.
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 Res (in press). Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
Lindroth AM, Park YJ, Matía V, Squatrito M (2020). The Mechanistic GEMMs of Oncogenic Histones. Hum Mol Genet 29, R226-R235. Publicación CNIO.
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. Publicación CNIO. Open Access
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). Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
de Lucas AG, Schuhmacher AJ, Oteo M, Romero E, Cámara JA, de Martino A, Arroyo AG, Morcillo MÁ, Squatrito M, Martinez-Torrecuadrada JL, Mulero F (2016). Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas. PLoS One 11, e0158634. Publicación CNIO. Open Access