Brain Cancer Dynamics & Therapy Translational Laboratory

One of the most intriguing and fatal characteristic of brain tumors is dissemination. This phenomenon can occur through dissemination of cancer cells from distant organs to the brain (brain metastases) or within the central nervous system (CNS) from primary brain tumors (medulloblastoma and ependymoma). The relevance to study brain metastatic disease relies in the absence of effective therapies, leading to severe disability and poor patient survival.

Therefore, our lab aims at understanding the dynamics of cancer cells and the mechanisms leading to CNS dissemination, the identification of biomarkers for early cancer detection using liquid biopsies and high-throughput genomics, and the development of novel treatment protocols using patient-derived models of brain metastatic disease.

We are a highly multidisciplinary and collaborative group combining the expertise of experimental biologists and clinicians from diverse disciplines in Neuro-Oncology, in the campus and beyond. Our translational projects take advantage of a large Brain Tumor Collection at the Biobanco-iMM CAML harbouring biological samples (tumor tissue, blood, plasma and cerebrospinal fluid) with detailed clinical annotation from pediatric and adult patients. In our lab we use cellular and molecular biology techniques, advanced microscopy, computational biology, and in vivo models of brain tumors. We are particularly interested in developing ex vivo organotypic models and patient-derived xenografts of brain tumors.

Check the page of the Centro de Investigação de Tumores Cerebrais here, for more information and to donate for our research.

Team

Areas

• Pediatric brain tumors: medulloblastoma and ependymoma
• Adult brain tumors: brain metastases and glioblastoma
• Mechanisms of cancer dissemination to the CNS
• Identification and validation of prognostic biomarkers
• Early cancer detection using liquid biopsies
• Preclinical testing of novel therapies using patient-derived models

Ongoing Projects

2023-2026 Developing Tools for Early Detection and Treatment of Brain Metastatic Cancer. Coordinator: Cláudia Faria. Funding Agency: HORIZON-WIDERA 2022.

2022-2025 Exploiting UBE2C as a prognostic marker and therapeutic target in human brain metastases. Coordinator: Cláudia Faria. Funding Agency: Fundação para a Ciência e a Tecnologia.

2022-2024 UBE2C as a prognostic marker and therapeutic target in patients with breast cancer brain metastases. Coordinator: Cláudia Faria. Funding Agency: Gilead Génese Award.

2021-2024 Unraveling the biology of metastatic pediatric brain tumors through genomics. Coordinator: Cláudia Faria. Funding Agency: Fundação Millenium bcp.

Awards

2023 Best Poster Award at III ASPIC- ASEICA international meeting (awarded to Carlos Custódia)

2023 Best Oral Presentation at III ASPIC-ASEICA International Meeting (awarded to Eunice Paisana)

2022 Honourable Mention from Prémio BIAL de Medicina Clínica 2022 (awarded to Cláudia Faria)

2022 Lídia Silva Santos Postdoctoral Achievement Award (awarded to Rita Cascão)

2022 Gilead Génese Award 2022 (awarded to Cláudia Faria)

2019 Best poster award at XI Congresso Nacional da Associação Portuguesa de Neuro-Oncologia (awarded to Eunice Paisana)

2018 Best poster award at the EurOPDX Workshop, Switzerland (awarded to Rita Cascão)

2018 Scholarship as Visiting Scientist at the Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada (awarded to Cláudia Faria)

2018 Ambassador of Bairrada Region for Research and Science (awarded to Cláudia Faria)

2017 Codman Award: Best oral presentation at the Congress of the Portuguese Neurosurgical Society (awarded to Cláudia Faria)

2017 Best First Year Oral Presentation at XI CAML PhD Students' Meeting (awarded to Eunice Paisana)

2016 D. Manuel de Mello Award (awarded to Cláudia Faria)

2016 Best poster award at IX Congresso Nacional da Associação Portuguesa de Neuro-Oncologia (awarded to Carlos Custódia)

2015 Fundação Millennium bcp Award (atribuído a Cláudia Faria)

2013 Phil Gold Scientist-in-Training Award (2nd prize for oral presentation) at the Montreal International Symposium on Angiogenesis and Metastasis (awarded to Cláudia Faria)

2012 Honourable Mention – Gallie-Bateman Competition and McMurrich Oral Presentation Competition, Department of Surgery, University of Toronto, Canada (awarded to Cláudia Faria)

Selected Publications

Our full list of publications is available here.

Muyas F, Rodriguez MJG, Cascão R, Afonso A, Sauer CM, Faria CC, Cortés-Ciriano I, & Flores I. (2024). The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients. Nature Communications, 15(1), 82. https://doi.org/10.1038/s41467-023-44287-8

Picard D, Felsberg J, Langini M, Stachura P, Qin N, Macas J, Reiss Y, Bartl J, Selt F, Sigaud R, Meyer FD, Stefanski A, Stühler K, Roque L, Roque R, Pandyra AA, Brozou T, Knobbe-Thomsen C, Plate KH, Roesch A, Milde T, Reifenberger G, Leprivier G, Faria CC*, Remke M.* (2023). Integrative multi-omics reveals two biologically distinct groups of pilocytic astrocytoma. Acta Neuropathologica, doi: 10.1007/s00401-023-02626-5. Online ahead of print. PMID: 37656187. *co-senior authors

Eunice Paisana, Rita Cascão, Carlos Custódia, Nan Qin, Daniel Picard, David Pauck, Tânia Carvalho, Pedro Ruivo, Clara Barreto, Delfim Doutel, José Cabeçadas, Rafael Roque, José Pimentel, José Miguéns, Marc Remke, João T. Barata and Claudia C. Faria (2023). UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease. Neurooncology Advances 5(1):vdad048.

Cruz N, Herculano-Carvalho M, Roque D, Faria CC, Cascão R, Ferreira HA, Reis CP, Matela N (2023). Highlighted Advances in Therapies for Difficult-To-Treat Brain Tumours Such as Glioblastoma. Pharmaceutics 15(3):928.

C.C. Faria*†, R. Cascão*, C. Custódia#, E. Paisana#, T. Carvalho, P. Pereira, R. Roque, J. Pimentel, J. Miguéns, I. Cortes-Ciriano, J.T. Barata (2022). Patient-derived models of brain metastases recapitulate human disseminated disease. Cell Reports Medicine 3 (5): 100623. * co-first authors; # co-second authors; † corresponding author.

Monteiro C, Miarka L, Perea-García M, Priego N, García-Gómez P, Álvaro-Espinosa L, de Pablos-Aragoneses A, Yebra N, Retana D, Baena P, Fustero-Torre C, Graña-Castro O, Troulé K, Caleiras E, Tezanos P, Muela P, Cintado E, Trejo JL, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez Á, Hernández-Lain A, Mazarico Gallego J, Ferrer I, Suárez R, Garrido-Martín EM, Paz-Ares L, Dalmasso C, Cohen-Jonathan Moyal E, Siegfried A, Hegarty A, Keelan S, Varešlija D, Young LS, Mohme M, Goy Y, Wikman H, Fernández-Alén J, Blasco G, Alcázar L, Cabañuz C, Grivennikov SI, Ianus A, Shemesh N, Faria CC, (…), Valiente M (2022). Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism. Nature Medicine 28(4):752-765.

N. Qin, E. Paisana, M. Langini, D. Picard, B. Malzkorn, C. Custódia, R. Cascão, F.-D. Meyer, L. Blümel, S. Göbbels, K. Taban, J. Bartl, N. Bechmann, C. Conrad, J. Gravemeyer, J.C. Becker, A. Stefanski, S. Puget, J.T. Barata, K. Stühler, U. Fischer, J. Felsberg, O. Ayrault, G. Reifenberger, A. Borkhardt, G. Eisenhofer, C.C. Faria* and M, Remke* (2022). Intratumoral heterogeneity of MYC drives medulloblastoma metastasis and angiogenesis. Neuro-Oncology 24(9):1509-1523. *co-senior authors

Noronha C, Ribeiro AS, Taipa R, Leitão D, Schmitt F, Reis J, Faria C.* and Paredes J.* (2022). PD-L1 tumor expression is associated with poor prognosis and systemic immunosuppression in glioblastoma. Journal of Neurooncology 156(3):453-464. *co-senior authors

Hendrikse LD, Haldipur P, Saulnier O, Millman J, Sjoboen AH, Erickson AW, Ong W, Gordon V, Coudière-Morrison L, Mercier AL, Shokouhian M, Suárez RA, Ly M, Borlase S, Scott DS, Vladoiu MC, Farooq H, Sirbu O, Nakashima T, Nambu S, Funakoshi Y, Bahcheli A, Diaz-Mejia JJ, Golser J, Bach K, Phuong-Bao T, Skowron P, Wang EY, Kumar SA, Balin P, Visvanathan A, Lee JJY, Ayoub R, Chen X, Chen X, Mungall KL, Luu B, Bérubé P, Wang YC, Pfister SM, Kim SK, Delattre O, Bourdeaut F, Doz F, Masliah-Planchon J, Grajkowska WA, Loukides J, Dirks P, Fèvre-Montange M, Jouvet A, French PJ, Kros JM, Zitterbart K, Bailey SD, Eberhart CG, Rao AAN, Giannini C, Olson JM, Garami M, Hauser P, Phillips JJ, Ra YS, de Torres C, Mora J, Li KKW, Ng HK, Poon WS, Pollack IF, López-Aguilar E, Gillespie GY, Van Meter TE, Shofuda T, Vibhakar R, Thompson RC, Cooper MK, Rubin JB, Kumabe T, Jung S, Lach B, Iolascon A, Ferrucci V, de Antonellis P, Zollo M, Cinalli G, Robinson S, Stearns DS, Van Meir EG, Porrati P, Finocchiaro G, Massimino M, Carlotti CG, Faria CC, (...) Taylor MD. (2022) Failure of human rhombic lip differentiation underlies medulloblastoma formation. Nature 609(7929):1021-1028.

Blümel L, Qin N, Berlandi J, Paisana E, Cascão R, Custódia C, Pauck D, Picard D, Langini M, Stühler K, Meyer FD, Göbbels S, Malzkorn B, Liebau MC, Barata JT, Jeibmann A, Kerl K, Erkek S, Kool M, Pfister SM, Johann PD, Frühwald MC, Borkhardt A, Reifenberger G, Faria CC, Fischer U, Hasselblatt M, Bartl J, Remke M. (2022). Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors. Cell Death and Disease 13 (9): 806.

Conde J, Pumroy RA, Baker C, Rodrigues T, Guerreiro A, Sousa BB, Marques MC, de Almeida BP, Lee S, Leites EP, Picard D, Samanta A, Vaz SH, Sieglitz F, Langini M, Remke M, Roque R, Weiss T, Weller M, Liu Y, Han S, Corzana F, Morais VA, Faria CC, Carvalho T, Filippakopoulos P, Snijder B, Barbosa-Morais NL, Moiseenkova-Bell VY, Bernardes GJL (2021) Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression. ACS Central Science 7(5):868-881.

Baroni LV, Sundaresan L, Heled A, Coltin H, Pajtler KW, Lin T, Merchant TE, McLendon R, Faria C, Buntine M, White CL, Pfister SM, Gilbert MR, Armstrong TS, Bouffet E, Kumar S, Taylor MD, Aldape KD, Ellison DW, Gottardo NG, Kool M, Korshunov A, Hansford JR, Ramaswamy V. (2021) Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q. Neuro-Oncology 23(8):1360-1370.

Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, (...) Northcott PA. (2021) Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. Journal Clinical Oncology 39(7):807-821.

Donovan LK, Delaidelli A, Joseph SK, Bielamowicz K, Fousek K, Holgado BL, Manno A, Srikanthan D, Gad AZ, Van Ommeren R, Przelicki D, Richman C, Ramaswamy V, Daniels C, Pallota JG, Douglas T, Joynt ACM, Haapasalo J, Nor C, Vladoiu MC, Kuzan-Fischer CM, Garzia L, Mack SC, Varadharajan S, Baker ML, Hendrikse L, Ly M, Kharas K, Balin P, Wu X, Qin L, Huang N, Stucklin AG, Morrissy AS, Cavalli FMG, Luu B, Suarez R, De Antonellis P, Michealraj A, Rastan A, Hegde M, Komosa M, Sirbu O, Kumar SA, Abdullaev Z, Faria CC, (...) Taylor MD. (2020) Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Nature Medicine 26(5):720-731.

Guerreiro Stucklin AS, Ryall S, Fukuoka K, Zapotocky M, Lassaletta A, Li C, Bridge T, Kim B, Arnoldo A, Kowalski PE, Zhong Y, Johnson M, Li C, Ramani AK, Siddaway R, Nobre LF, de Antonellis P, Dunham C, Cheng S, Boué DR, Finlay JL, Coven SL, de Prada I, Perez-Somarriba M, Faria CC, (...) Hawkins C. (2019) Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nature Communications 25;10(1):4343.

Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Nageswara Rao AA, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, (...) Taylor MD. (2019) Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma. Nature 574(7780):707-711.

Bertrand KC, Faria CC, Skowron P, Luck A, Garzia L, Wu X, Agnihotri S, Smith CA, Taylor MD, Mack SC, Rutka JT (2018) A functional genomics approach to identify pathways of drug resistance in medulloblastoma. Acta Neuropathologica Communications 6(1):146.

Gonçalves CS, Vieira de Castro J, Pojo M, Martins EP, Queirós S, Chautard E, Taipa R, Pires MM, Pinto AA, Pardal F, Custódia C, Faria CC, Clara C, Reis RM, Sousa N, Costa BM. (2018) WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma. Theranostics 8(17):4805-4823.

Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, López-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, (...) Taylor MD. (2017) Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell 31(6):737-754.

Faria CC, Golbourn BJ, Dubuc AM, Remke M, Diaz RJ, Agnihotri S, Luck A, Sabha N, Olsen S, Wu X, Garzia L, Ramaswamy V, Mack SC, Wang X, Leadley M, Reynaud D, Ermini L, Post M, Northcott PA, Pfister SM, Croul SE, Kool M, Korshunov A, Smith CA, Taylor MD, Rutka JT. (2015) Foretinib is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma. Cancer Research 1;75(1):134-46.

Faria CC, Agnihotri S, Mack SC, Golbourn BJ, Diaz RJ, Olsen S, Bryant M, Bebenek M, Wang X, Bertrand KC, Kushida M, Head R, Clark I, Dirks P, Smith CA, Taylor MD, Rutka JT. (2015) Identification of alsterpaullone as a novel small molecule to inhibitor to target Group 3 medulloblastoma. Oncotarget 28;6(25):21718-29.

Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M, Luu B, Yao Y, Wang X, Dubuc AM, Garzia L, Peacock J, Mack SC, Wu X, Rolider A, Morrissy AS, Cavalli FM, Jones DT, Zitterbart K, Faria CC et al. (2014) Cytogenetic prognostication within medulloblastoma subgroups. Journal of Clinical Oncology 32(9):886-96.

Ramaswamy V, Remke M, Bouffet E, Faria CC, et al. (2013). Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncology 14(12):1200-7.