Suvà Lab

"Genetic and non-genetic determinants of single-cell programs in human gliomas"

Phone: 617-726-5156

Overview

Mario L. Suvà, M.D., Ph.D

Assistant Professor of Pathology, Harvard Medical School
Assistant Molecular Pathologist, Massachusetts General Hospital

Molecular Pathology Unit
Massachusetts General Hospital
149 13th Street, 6th Floor
Charlestown, MA 02129
Phone: 617-726-6247

Overview

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.

Group Members

Biography

Affiliations

lab Websites

Mariella Filbin, MD, PhD Fellow
McKenzie Shaw, Research Technician II
Christine Hebert, Research Technician II
Cyril Neftel, MD, PhD student
Kristof Egervari, MD Visiting Fellow

 

 

 

 

 

 

 

 

 

Publications

Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suvà ML, Bernstein BE.  Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016; 529(7584):110-4.


Louis DN, Suvà ML, et al. Primary Glioblastoma, IDH wild-type. WHO Classification of Tumors of the Central Nervous System, revised 4th edition, 2016.
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*. Single-cell RNA-seq highlights intra-tumoral heterogeneity in primary glioblastoma. Science. 2014; 344(6190):1396-401. (*co-senior authorship)


Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Riggi N, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek A, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells. Cell. 2014; 157(3):525-7 (co-first authored).


Rheinbay E1, 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. Chromatin profiles reveal an aberrant transcription factor network connected to Wnt signaling and essential for glioblastoma stem cell maintenance. Cell Reports. 2013; 3(5):1567-79. (co-first authored).


Suvà ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science. 2013; 339(6127):1567-70.

Phone: 617-726-5156

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