Massimo Squatrito Group Leader
T +34 (+34) 917 328 000 (Ext 3850)
msquatrito@cnio.es

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 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 the treatment of brain tumours.

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Oldrini B, Schuhmacher AJ, Squatrito M (2015). Take It Down a NOTCH in Forebrain tumors.. Cancer Cell 28, 681-682.
• Ozawa T, Riester M, Cheng YK, Huse JT, Squatrito M, Helmy K, Charles N, Michor F, Holland EC. (2014). Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma.. Cancer Cell 26, 288-300.
• Vivanco I, Chen ZC, Tanos B, Oldrini B, Hsieh WY, Yannuzzi N, Campos C, Mellinghoff IK (2014). A kinase-independent function of AKT promotes cancer cell survival.. Elife (in press).
• Malatesta M, Steinhauer C, Mohammad F, Pandey DP, Squatrito M, Helin K (2013). Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation.. Cancer Res 73, 6323-6333.