149 13th Street – 6010
Charlestown, MA 02129
Mario Luca Suvà, MD, PhD
Associate Professor of Pathology
Massachusetts General Hospital
Associate Molecular Pathologist
Massachusetts General Hospital
Broad Institute of MIT and Harvard
Co-Leader, Neuro-Oncology Program, DF/HCC
Co-Leader, Cancer Program, Harvard Stem Cell Institute
Center for Cancer Research
Explore the Suvà Lab
Our laboratory is focused on the biology of brain tumors, in particular diffuse gliomas in adults and children. We study primary human samples at single-cell resolution using transcriptomic and genomic approaches. We reconstruct the cellular composition of patient tumors and relate it to genetic mutations. We model how brain cancer cells exploit developmental programs to establish distinct cellular states. Additionally, the laboratory investigates how genetic events affecting genes involved in chromatin regulation rewire cancer cells’ identities to contribute
to cellular transformation. We seek to identify common programs that would offer novel therapeutic options in these dismal diseases.
Heterogeneity in brain tumors assessed at single-cell level
We are deploying cutting-edge single-cell genomic, epigenomic and transcriptional profiling to clinical samples. Our unique approach allows us for the first time to relate genotype to phenotype at single-cell resolution in clinical tumor specimens. Through our efforts, we are redefining our understanding of malignant cell subpopulations in glioblastoma, oligodendroglioma, astrocytoma, diffuse intrinsic pontine glioma, medulloblastoma and synovial sarcoma. In addition, our single-cell genomics efforts are providing invaluable insights into myeloid cells and T cell programs in clinical tumors.
Targeting Cellular States in Glioblastoma
Although cancer is a genetic disease, malignancies are associated with aberrations in gene expression related to both cancer cell-intrinsic and -extrinsic factors. Genetic, epigenetic and microenvironmental cues are integrated at the cellular level into states of expression that govern many critical facets of tumor biology, such as tumor growth, metastasis, and resistance to treatment. A better understanding of the precise determinants of the cellular states that drive cancer is a critical goal with broad implications for oncology. Our lab is pursuing the goal of targeting the four cellular states of glioblastoma that our single-cell RNA-sequencing efforts have uncovered. To this end, we established faithful models of cellular states observed in patients, dissect the rules governing cellular transitions using single-cell barcodes and leverage genome editing and small molecules targeting defined pathways to identify specific vulnerabilities for glioblastoma.
Neftel C†, Laffy J†, Filbin MG†, Hara T†, Shore ME, Rahme GJ, Richman AR, Silverbush D, Shaw ML, Hebert CM, Dewitt J, Gritsch S, Perez L, Gonzalez Castro LN, …, Louis DN, Regev A, Bernstein BE, Tirosh I*, Suvà ML*. An integrative model of cellular states, plasticity and genetics for glioblastoma. Cell. 2019 Aug 8;178(4):835-849.
Filbin MG†, Tirosh I†, Hovestadt V†, Shaw ML, Escalante LE, …, 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 Apr 20;360(6386).
Venteicher AS†, Tirosh I†, Hebert C, Yizhak K, Neftel C, Filbin MG, Hovestadt V, ..., Cahill DP, Rozenblatt-Rosen O, Louis DN, Bernstein BE, Regev A*, Suvà ML*. Decoupling genetics, lineages and micro-environment in IDH-mutant gliomas by single-cell RNA-seq. Science. 2017 Mar 31; 55(6332).
Tirosh I†, Venteicher AS†, Hebert C, Escalante LE, Patel AP, Yizhak K, Fisher JM, ..., 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 Nov 10;539(7628).
Mario Luca Suvà, MD, PhDPrincipal Investigator
- Lilly Bussema, BS
- Nick Gonzalez-Castro, MD, PhD
- Simon Gritsch, MD, PhD
- Toshiro Hara, PhD
- Masashi Nomura, MD, PhD
- Liz Perez*
- Dana Silverbush, PhD
- Hannah Weisman, BS
- Yixin Zhang, BS