Photo of Mariella G. Filbin,  MD, PhD

Mariella G. Filbin, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-5993


mariella.filbin@childrens.harvard.edu

Mariella G. Filbin, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Pediatrics, Harvard Medical School
  • Attending Physician, Pediatric Oncology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research focuses on pediatric brain tumors, particularly the lethal high-grade gliomas and malignant embryonal brain tumors that are in greatest need of therapeutic improvements. I am especially interested in how the specific developmental and cellular contexts in which tumorigenic mutations arise shape the cellular hierarchy of the resulting tumors. This developmental “fingerprint” can then be used to design novel therapies that either enable differentiation of tumor cells so they are no longer proliferating or induce tumor cell death. In my studies I am combining single-cell genetics and transcriptomics with gene editing-, epigenetic-, stem cell- and pharmacologic methods to identify these cellular states, hierarchies and networks underlying tumorigenesis, with the goal of establishing new druggable targets.

Publications from Harvard Catalyst Profiles

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  • Przystal JM, Cosentino CC, Yadavilli S, Zhang J, Laternser S, Bonner ER, Prasad R, Dawood AA, Lobeto N, Chong WC, Biery MC, Myers C, Olson JM, Panditharatna EA, Kritzer B, Mourabit S, Vitanza NA, Filbin MG, De Iuliis GN, Dun MD, Koschmann C, Cain J, Grotzer MA, Waszak SM, Mueller S, Nazarian J. Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas. 2022. PubMed
  • Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H, Schultz LM, Richards RM, Jiang L, Barsan V, Mancusi R, Geraghty AC, Good Z, Mochizuki AY, Gillespie SM, Toland AMS, Mahdi J, Reschke A, Nie EH, Chau IJ, Rotiroti MC, Mount CW, Baggott C, Mavroukakis S, Egeler E, Moon J, Erickson C, Green S, Kunicki M, Fujimoto M, Ehlinger Z, Reynolds W, Kurra S, Warren KE, Prabhu S, Vogel H, Rasmussen L, Cornell TT, Partap S, Fisher PG, Campen CJ, Filbin MG, Grant G, Sahaf B, Davis KL, Feldman SA, Mackall CL, Monje M. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 2022; 603:934-941. PubMed
  • Lötsch D, Kirchhofer D, Englinger B, Jiang L, Okonechnikov K, Senfter D, Laemmerer A, Gabler L, Pirker C, Donson AM, Bannauer P, Korbel P, Jaunecker CN, Hübner JM, Mayr L, Madlener S, Schmook MT, Ricken G, Maaß K, Grusch M, Holzmann K, Grasl-Kraupp B, Spiegl-Kreinecker S, Hsu J, Dorfer C, Rössler K, Azizi AA, Foreman NK, Peyrl A, Haberler C, Czech T, Slavc I, Filbin MG, Pajtler KW, Kool M, Berger W, Gojo J. Targeting fibroblast growth factor receptors to combat aggressive ependymoma. Acta Neuropathol 2021. PubMed
  • Alencastro Veiga Cruzeiro G, Rota C, Hack OA, Segal R, Filbin MG. Understanding the epigenetic landscape and cellular architecture of childhood brain tumors. Neurochem. Int. 2021; 144:104940. PubMed
  • Tsai JW, Manoharan N, Alexandrescu S, Zimmerman MA, Scully J, Chordas C, Clymer J, Wright KD, Filbin M, Ullrich NJ, Marcus KJ, Haas-Kogan D, Chi SN, Bandopadhayay P, Yeo KK. Outcomes after first relapse of childhood intracranial ependymoma. Pediatr Blood Cancer 2021. PubMed
  • Panwalkar P, Tamrazi B, Dang D, Chung C, Sweha S, Natarajan SK, Pun M, Bayliss J, Ogrodzinski MP, Pratt D, Mullan B, Hawes D, Yang F, Lu C, Sabari BR, Achreja A, Heon J, Animasahun O, Cieslik M, Dunham C, Yip S, Hukin J, Phillips JJ, Bornhorst M, Griesinger AM, Donson AM, Foreman NK, Garton HJL, Heth J, Muraszko K, Nazarian J, Koschmann C, Jiang L, Filbin MG, Nagrath D, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Allis CD, Chinnaiyan AM, Lunt SY, Blüml S, Judkins AR, Venneti S. Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas. Sci Transl Med 2021; 13:eabc0497. PubMed
  • Chen CCL, Deshmukh S, Jessa S, Hadjadj D, Lisi V, Andrade AF, Faury D, Jawhar W, Dali R, Suzuki H, Pathania M, A D, Dubois F, Woodward E, Hébert S, Coutelier M, Karamchandani J, Albrecht S, Brandner S, De Jay N, Gayden T, Bajic A, Harutyunyan AS, Marchione DM, Mikael LG, Juretic N, Zeinieh M, Russo C, Maestro N, Bassenden AV, Hauser P, Virga J, Bognar L, Klekner A, Zapotocky M, Vicha A, Krskova L, Vanova K, Zamecnik J, Sumerauer D, Ekert PG, Ziegler DS, Ellezam B, Filbin MG, Blanchette M, Hansford JR, Khuong-Quang DA, Berghuis AM, Weil AG, Garcia BA, Garzia L, Mack SC, Beroukhim R, Ligon KL, Taylor MD, Bandopadhayay P, Kramm C, Pfister SM, Korshunov A, Sturm D, Jones DTW, Salomoni P, Kleinman CL, Jabado N. Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis. Cell 2020; 183:1617-1633.e22. PubMed
  • Dorfer C, Czech T, Gojo J, Hosmann A, Peyrl A, Azizi AA, Kasprian G, Dieckmann K, Filbin MG, Haberler C, Roessler K, Slavc I. Infiltrative gliomas of the thalamus in children: the role of surgery in the era of H3 K27M mutant midline gliomas. Acta Neurochir (Wien) 2020. PubMed
  • Manoharan N, Choi J, Chordas C, Zimmerman MA, Scully J, Clymer J, Filbin M, Ullrich NJ, Bandopadhayay P, Chi SN, Yeo KK. Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma. J. Neurooncol. 2020. PubMed
  • Torre M, Vasudevaraja V, Serrano J, DeLorenzo M, Malinowski S, Blandin AF, Pages M, Ligon AH, Dong F, Meredith DM, Nasrallah MP, Horbinski C, Dahiya S, Ligon KL, Santi M, Ramkissoon SH, Filbin MG, Snuderl M, Alexandrescu S. Molecular and clinicopathologic features of gliomas harboring NTRK fusions. Acta Neuropathol Commun 2020; 8:107. PubMed
  • Panditharatna E, Filbin MG. The growing role of epigenetics in childhood cancers. Curr Opin Pediatr 2019. PubMed
  • Nagaraja S, Quezada MA, Gillespie SM, Arzt M, Lennon JJ, Woo PJ, Hovestadt V, Kambhampati M, Filbin MG, Suva ML, Nazarian J, Monje M. Histone Variant and Cell Context Determine H3K27M Reprogramming of the Enhancer Landscape and Oncogenic State. Mol Cell 2019; 76:965-980.e12. PubMed
  • Jessa S, Blanchet-Cohen A, Krug B, Vladoiu M, Coutelier M, Faury D, Poreau B, De Jay N, Hébert S, Monlong J, Farmer WT, Donovan LK, Hu Y, McConechy MK, Cavalli FMG, Mikael LG, Ellezam B, Richer M, Allaire A, Weil AG, Atkinson J, Farmer JP, Dudley RWR, Larouche V, Crevier L, Albrecht S, Filbin MG, Sartelet H, Lutz PE, Nagy C, Turecki G, Costantino S, Dirks PB, Murai KK, Bourque G, Ragoussis J, Garzia L, Taylor MD, Jabado N, Kleinman CL. Stalled developmental programs at the root of pediatric brain tumors. Nat Genet 2019; 51:1702-1713. PubMed
  • Anastas JN, Zee BM, Kalin JH, Kim M, Guo R, Alexandrescu S, Blanco MA, Giera S, Gillespie SM, Das J, Wu M, Nocco S, Bonal DM, Nguyen QD, Suva ML, Bernstein BE, Alani R, Golub TR, Cole PA, Filbin MG, Shi Y. Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG. Cancer Cell 2019; 36:528-544.e10. PubMed
  • Kim GB, Rincon Fernandez Pacheco D, Saxon D, Yang A, Sabet S, Dutra-Clarke M, Levy R, Watkins A, Park H, Abbasi Akhtar A, Linesch PW, Kobritz N, Chandra SS, Grausam K, Ayala-Sarmiento A, Molina J, Sedivakova K, Hoang K, Tsyporin J, Gareau DS, Filbin MG, Bannykh S, Santiskulvong C, Wang Y, Tang J, Suva ML, Chen B, Danielpour M, Breunig JJ. Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements. Cell 2019; 179:251-267.e24. PubMed
  • Lin GL, Nagaraja S, Filbin MG, Suvà ML, Vogel H, Monje M. Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma. Acta Neuropathol Commun 2018; 6:51. PubMed
  • Filbin MG, Sturm D. Gliomas in Children. Semin Neurol 2018; 38:121-130. PubMed
  • Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Escalante LE, Mathewson ND, Neftel C, Frank N, Pelton K, Hebert CM, Haberler C, Yizhak K, Gojo J, Egervari K, Mount C, van Galen P, Bonal DM, Nguyen QD, Beck A, Sinai C, Czech T, Dorfer C, Goumnerova L, Lavarino C, Carcaboso AM, Mora J, Mylvaganam R, Luo CC, Peyrl A, Popović M, Azizi A, Batchelor TT, Frosch MP, Martinez-Lage M, Kieran MW, Bandopadhayay P, Beroukhim R, Fritsch G, Getz G, Rozenblatt-Rosen O, Wucherpfennig KW, Louis DN, Monje M, Slavc I, Ligon KL, Golub TR, Regev A, Bernstein BE, Suvà ML. Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science 2018; 360:331-335. PubMed
  • Juratli TA, Qin N, Cahill DP, Filbin MG. Molecular pathogenesis and therapeutic implications in pediatric high-grade gliomas. Pharmacol Ther 2017. PubMed
  • Ramkissoon SH, Bandopadhayay P, Hwang J, Ramkissoon LA, Greenwald NF, Schumacher SE, O'Rourke R, Pinches N, Ho P, Malkin H, Sinai C, Filbin M, Plant A, Bi WL, Chang MS, Yang E, Wright KD, Manley PE, Ducar M, Alexandrescu S, Lidov H, Delalle I, Goumnerova LC, Church AJ, Janeway KA, Harris MH, MacConaill LE, Folkerth RD, Lindeman NI, Stiles CD, Kieran MW, Ligon AH, Santagata S, Dubuc AM, Chi SN, Beroukhim R, Ligon KL. Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors. 2017. PubMed
  • Venteicher AS, Tirosh I, Hebert C, Yizhak K, Neftel C, Filbin MG, Hovestadt V, Escalante LE, Shaw ML, Rodman C, Gillespie SM, Dionne D, Luo CC, Ravichandran H, Mylvaganam R, Mount C, Onozato ML, Nahed BV, Wakimoto H, Curry WT, Iafrate AJ, Rivera MN, Frosch MP, Golub TR, Brastianos PK, Getz G, Patel AP, Monje M, Cahill DP, Rozenblatt-Rosen O, Louis DN, Bernstein BE, Regev A, Suvà ML. Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science 2017. PubMed
  • Filbin MG, Suvà ML. Glioma Genomics and Epigenomics: Arriving at the Start and Knowing it for the First Time. Annu Rev Pathol 2016. PubMed
  • Tirosh I, Venteicher AS, Hebert C, Escalante LE, Patel AP, Yizhak K, Fisher JM, Rodman C, Mount C, Filbin MG, Neftel C, Desai N, Nyman J, Izar B, Luo CC, Francis JM, Patel AA, Onozato ML, Riggi N, Livak KJ, Gennert D, Satija R, Nahed BV, Curry WT, Martuza RL, Mylvaganam R, Iafrate AJ, Frosch MP, Golub TR, Rivera MN, Getz G, Rozenblatt-Rosen O, Cahill DP, Monje M, Bernstein BE, Louis DN, Regev A, Suvà ML. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature 2016. PubMed
  • Filbin MG, Segal RA. How neuronal activity regulates glioma cell proliferation. 2015. PubMed
  • Filbin MG, Stiles CD. Of Brains and Blood: Developmental Origins of Glioma Diversity? Cancer Cell 2015; 28:403-4. PubMed
  • Chadwick EJ, Yang DP, Filbin MG, Mazzola E, Sun Y, Behar O, Pazyra-Murphy MF, Goumnerova L, Ligon KL, Stiles CD, Segal RA. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies. 2015. PubMed
  • Filbin MG, Dabral SK, Pazyra-Murphy MF, Ramkissoon S, Kung AL, Pak E, Chung J, Theisen MA, Sun Y, Franchetti Y, Sun Y, Shulman DS, Redjal N, Tabak B, Beroukhim R, Wang Q, Zhao J, Dorsch M, Buonamici S, Ligon KL, Kelleher JF, Segal RA. Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: new therapeutic opportunities. Nat Med 2013; 19:1518-23. PubMed
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