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Research at Mass General
Mario L. Suvà, M.D., Ph.D
Assistant Professor of Pathology, Harvard Medical SchoolAssistant Molecular Pathologist, Massachusetts General Hospital
Molecular Pathology UnitMassachusetts General Hospital149 13th Street, 6th FloorCharlestown, MA 02129Phone: 617-726-6247
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 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.
Gliomas heterogeneity assessed at single-cell level
We are deploying cutting-edge single-cell genomic 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 glioma specimens. Through our efforts, we are redefining our understanding of glioblastoma, oligodendroglioma, astrocytoma and diffuse intrinsic pontine glioma.
Annotation of functional genomic elements in secondary glioblastoma, pediatric glioblastoma and oligodendroglioma
We have previously performed deep chromatin landscape profiling and analysis of primary glioblastoma models and have utilized this information to reconstruct functionally validated network models. We are applying similar approaches to genetically defined primary cultures of IDH1 mutant glioblastoma, H3F3A mutant pediatric glioblastoma and IDH1 mutant oligodendroglioma obtained through our collaborations with the MGH Brain Tumor Center.
Targeting neurodevelopmental programs in primary human glioblastoma stem cells
Our work has identified neurodevelopmental transcription factors as master regulators of a stem-like state in glioblastoma and reconstructed a transcriptional network model. Our lab is utilizing genome-editing technologies to generate functional knock-out of critical nodes in the network to identify novel dependencies in glioblastoma and assess novel therapeutic options.
Mariella Filbin, MD, PhD FellowMcKenzie Shaw, Research Technician IIChristine Hebert, Research Technician IICyril Neftel, MD, PhD studentKristof Egervari, MD Visiting Fellow
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.
Louis DN, Suva ML et al. Primary Glioblastoma, IDH wild-type. In:
WHO Classification of Tumours of the Central Nervous System, Revised. Fourth Edition 2016
Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K. (Not yet in PubMed)
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suvà ML, Regev A, Bernstein BE. Science. 2014 Jun 20;344(6190):1396-401.
Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Cell. 2014 Apr 24;157(3):580-94.
An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE. Cell Rep. 2013 May 30;3(5):1567-79.
Epigenetic reprogramming in cancer. Suvà ML, Riggi N, Bernstein BE. Science. 2013 Mar 29;339(6127):1567-70.
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