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Dissecting human gliomas by single-cell genomics
April 3, 2019 @ 3:30 pm - 5:00 pm
Laboratory of Genetics Spring Colloquium Series 2019
Research area: http://suvalab.mgh.harvard.edu
The Suvà laboratory is focused on the biology of brain tumors, in particular diffuse gliomas in adults and children. We dissect how cellular heterogeneity and plasticity contribute to tumor properties. We study primary human samples at single-cell resolution and establish genetically and epigenetically relevant cellular models from patient tumors. We model how brain cancer cells exploit their plasticity to establish distinct epigenetic programs. We seek to identify common programs that would offer novel therapeutic options in these dismal diseases.
Brief bio:
Dr. Mario Suva trained in Switzerland, where he also received his PhD for work in the biology of cancer stem cells in gliomas and sarcomas. He is an Assistant Professor of Pathology at Harvard Medical School where he also serves as a faculty member for the Biological and Biomedical Science Program and for the Harvard Stem Cell Institute. Additionally, he is a member of the Neuro-oncology Program at the Harvard Cancer Center and of the Epigenomics, Cancer and Cell Circuits Programs at the Broad Institute. He has received multiple awards including the Howard Goodman Award (2017), the Weil Award (2014) for best work in experimental neuropathology by the American Association of Neuropathologists and the Adult Basic Research Award from the Society for Neuro-oncology.
Publications (selected):
| Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Keskin DB et al. Nature. 2019 Jan;565(7738):234-239. doi: 10.1038/s41586-018-0792-9. |
| Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Bunse L, et al., Nat Med. 2018 Aug;24(8):1192-1203. doi: 10.1038/s41591-018-0095-6. |
| A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment. Griveau A et al., Cancer Cell. 2018 May 14;33(5):874-889.e7. doi: 10.1016/j.ccell.2018.03.020. |
| Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Filbin MG, …, Suvà ML. Science. 2018 Apr 20;360(6386):331-335. doi: 10.1126/science.aao4750. |
| Toward methylation-based classification of central nervous system tumors. Hegi ME, Kleihues P, Wen PY, Suvà ML. Neuro Oncol. 2018 Apr 9;20(5):579-581. doi: 10.1093/neuonc/noy023. |
| Dissecting human gliomas by single-cell RNA sequencing. Tirosh I, Suvà ML. Neuro Oncol. 2018 Jan 10;20(1):37-43. doi: 10.1093/neuonc/nox126. Review. |
| Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing. Tang Q, Iyer S, Lobbardi R, Moore JC, Chen H, Lareau C, Hebert C, Shaw ML, Neftel C, Suva ML, Ceol CJ, Bernards A, Aryee M, Pinello L, Drummond IA, Langenau DM. J Exp Med. 2017 Oct 2;214(10):2875-2887. doi: 10.1084/jem.20170976. E |
| Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression. Yu D, Khan OF, Suvà ML, Dong B, Panek WK, Xiao T, Wu M, Han Y, Ahmed AU, Balyasnikova IV, Zhang HF, Sun C, Langer R, Anderson DG, Lesniak MS. Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6147-E6156. doi: 10.1073/pnas.1701911114. |
| Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. 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. Science. 2017 Mar 31;355(6332). pii: eaai8478. doi: 10.1126/science.aai8478. |
| Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Wang X, Yang K, Xie Q, Wu Q, Mack SC, Shi Y, Kim LJY, Prager BC, Flavahan WA, Liu X, Singer M, Hubert CG, Miller TE, Zhou W, Huang Z, Fang X, Regev A, Suvà ML, Hwang TH, Locasale JW, Bao S, Rich JN. Nat Neurosci. 2017 May;20(5):661-673. doi: 10.1038/nn.4537. |
| Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance. Liau BB, Sievers C, Donohue LK, Gillespie SM, Flavahan WA, Miller TE, Venteicher AS, Hebert CH, Carey CD, Rodig SJ, Shareef SJ, Najm FJ, van Galen P, Wakimoto H, Cahill DP, Rich JN, Aster JC, Suvà ML, Patel AP, Bernstein BE. Cell Stem Cell. 2017 Feb 2;20(2):233-246.e7. doi: 10.1016/j.stem.2016.11.003. |
| IMPs: an RNA-binding protein family that provides a link between stem cell maintenance in normal development and cancer. Degrauwe N, Suvà ML, Janiszewska M, Riggi N, Stamenkovic I. Genes Dev. 2016 Nov 15;30(22):2459-2474. Review. |
| Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. 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. Nature. 2016 Nov 10;539(7628):309-313. doi: 10.1038/nature20123. |
| The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let-7 Target Gene Silencing. Degrauwe N, Schlumpf TB, Janiszewska M, Martin P, Cauderay A, Provero P, Riggi N, Suvà ML, Paro R, Stamenkovic I. Cell Rep. 2016 May 24;15(8):1634-47. doi: 10.1016/j.celrep.2016.04.086. |
| Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time. Filbin MG, Suvà ML. Annu Rev Pathol. 2016 May 23;11:497-521. doi: 10.1146/annurev-pathol-012615-044208. Review. |
| Insulator dysfunction and oncogene activation in IDH mutant gliomas. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suvà ML, Bernstein BE. Nature. 2016 Jan 7;529(7584):110-4. doi: 10.1038/nature16490. Epub 2015 Dec 23. |
| Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Flynn RL, Cox KE, Jeitany M, Wakimoto H, Bryll AR, Ganem NJ, Bersani F, Pineda JR, Suvà ML, Benes CH, Haber DA, Boussin FD, Zou L. Science. 2015 Jan 16;347(6219):273-7. doi: 10.1126/science.1257216. |
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