BBS Faculty Member - Bradley Bernstein

Bradley Bernstein

Department of Pathology
Massachusetts General Hospital, Harvard Medical School and Broad Institute

Massachusetts General Hospital
Simches Research Building, CPZN 8234
185 Cambridge St.
Boston, MA 02114
Tel: 617-726-6906
Fax: 617-643-3566
Lab Members: 11 postdoctoral fellows, 2 graduate students, 2 technicians
Visit my lab page here.

Though much of what defines a human is encoded in the sequence of our DNA, many additional factors influence how this genetic information is manifest. For example, heritable epigenetic information contained within chromatin, the higher-order structure that packages the genome, has critical functions during embryonic development and can contribute to the pathogenesis of disease. Our laboratory applies high-throughput sequencing-based technologies to characterize chromatin structure genome-wide in human and mouse. In addition to advancing technology and providing unprecedented global views of mammalian chromatin, this work has led to an appreciation of the role of large-scale chromatin structures, or ‘domains’, in regulating developmental genes. In differentiated cells, chromatin domains marked by either ‘active’ or ‘repressive’ histone modifications maintain expression or repression of key developmental genes (‘master regulators’). However, in pluripotent ES cells, chromatin domains enriched for both active and repressive modifications repress developmental genes while maintaining their potential for subsequent activation. Current projects in the lab are are focused on these 'bivalent' domains with the goals of understanding their initial establishment, their higher-order structure, and their roles in ES cell pluripotency and epigenetic regulation. Similar approaches are also being used to characterize chromatin modifications in adult stem cells and cancer models. Our long-term goal is to achieve a systems level understanding of chromatin regulation during development, and how chromatin mis-regulation contributes to human disease.

Last Update: 8/6/2015


For a complete listing of publications click here.



Suva ML, Rheinbay E, Gillespie SM, Wakimoto H, Cahill DP, Nashed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A, Bernstein BE. Reconstructing and programming the tumor propagating potential of glioblastoma stem-like cells. Cell. 157: 580-594, 2014.

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, Suva ML, Regev A, Bernstein BE. Single Cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 344:1396-1401, 2014.

Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T-cell acute lymphoblastic leukemia. Nat Genet. 46: 364-70, 2014.

Suva ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science. 339:1567-70, 2013.

Rheinbay E, Suva ML, Gillespie SM, Wakimoto H, Patel AP, 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. 3:1567–79, 2013.

Zhu J, Adli M, Zou JY, Verstappen G, Coyne Michael, Zhang X, Durham T, Miri M, Deshpande V, De Jager PL, Bennett DA, Houmard JA, Muoio DM, Onder TT, Camahort R, Cowan CA, Meissner A, Epstein CB, Shoresh N, Bernstein BE. Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell. 152:642–654, 2013.

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