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Bradley E. Bernstein

Johnstone SE, Reyes A, Qi Y, Adriaens C, Hegazi E, Pelka K, Chen J, Zou LS, Drier Y, Hecht V, Shoresh N, Selig MK, Lareau C, Iyer S, Nguyen SC, Joyce EF, Hacohen N, Irizarry RA, Zhang B, Aryee MJ, Bernstein BE. Large-scale topological changes restrain malignant progression in colorectal cancer. Cell 2020; 182:1474-1489. NIHMS 1622878 (PMCID in progress).

van Galen P, Hovestadt V, Wadsworth MH, Hughes TK, Griffin GK, Battaglia S, Verga JA, Stephansky J, Pastika TJ, Lombardi Story J, Pinkus GS, Pozdnyakova O, Galinsky I, Stone RM, Graubert TA, Shalek AK, Aster JC, Lane AA, Bernstein BE. Single-cell RNA-Seq reveals AML hierarchies relevant to disease progression and immunity. Cell 2019; 176:1265-81. PMC6515904.

Flavahan WA, Drier Y, Johnstone SE, Hemming ML, Tarjan DR, Hegazi E, Shareef SJ, Javed NM, Raut CP, Eschle BK, Gokhale PC, Hornick JL, Sicinska ET, Demetri GD, Bernstein BE. Altered chromosomal topology drives oncogenic programs in SDH-deficient GIST. Nature 2019; 575:229-33. PMC6913936.

Bradley E. Bernstein, M.D., Ph.D.

Bradley E. Bernstein is an institute member at the Broad Institute and a professor in the Department of Pathology at Massachusetts General Hospital and Harvard Medical School. Bernstein is the director of the Gene Regulation Observatory (GRO). He co-directs the Broad’s Epigenomics Program and interacts extensively with the Cell Circuits Program, the Cancer Program, and the Klarman Cell Observatory.

The GRO launched in 2020, and brings together a community to investigate the regulation of context-specific gene expression within cells, from transcription factors, chromatin, and nuclear architecture to the functional elements, regulatory interactions, and circuits that control cell states and transitions. The GRO drives progress by initiating and coordinating flagship projects; nucleating communities across scientific disciplines; working with the Cell Circuits and Epigenomics Programs; pioneering the creation of powerful new tools; and ensuring that robust single-cell capabilities are available to the Broad community.

Bernstein’s research focuses on epigenetics — changes in gene activity governed by influences outside the genes themselves — and specifically how modifications to the protein scaffold called chromatin contribute to mammalian development and human cancer. Bernstein’s laboratory is characterizing epigenetic mechanisms that underlie stem cells’ ability to give rise to almost any kind of cell, while also exploring how epigenetic mechanisms contribute to malignant transformation and therapeutic resistance. His work is notable for the discovery of epigenetic mechanisms in pluripotent stem cells, the systematic identification of enhancer “switches” in the human genome that coincide with DNA sequence variants associated with common diseases, and the characterization of epigenetic aberrations that underlie certain forms of cancer.

Bernstein oversees a production center for the NHGRI-sponsored ENCODE project, which seeks to catalog all of the working parts of the genome, and to understand how their functional interactions give rise to the diverse cell and tissue types in a human. His group also investigates epigenetic landscapes of human tumors, including glioblastoma, leukemia, and Ewing sarcoma, and has identified epigenetic mechanisms that underlie malignant transformation, tumor propagation, and therapeutic resistance. This work benefits from an outstanding team of basic, clinical, and production-oriented scientists in the Epigenomics Program, and extensive collaborations with computational scientists and disease researchers at the Broad Institute and partner hospitals.

After receiving his M.D. and Ph.D., Bernstein completed a residency in clinical pathology at Brigham and Women’s Hospital. He carried out postdoctoral research at Harvard University with Stuart Schreiber and also collaborated extensively with Eric Lander. He joined the faculty of Massachusetts General Hospital and Harvard Medical School in 2005.

Bernstein’s honors and awards include a Howard Hughes Postdoctoral Research Fellowship for Physicians, a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, a junior faculty award from the Culpeper Foundation, election into the American Society for Clinical Investigation, and an Early Career Scientist award from the Howard Hughes Medical Institute. Bernstein’s work was featured in a 2019 episode of the TheoryLab podcast from the American Cancer Society.

Bernstein received his B.S. from Yale University in physics and his M.D. and Ph.D. from the University of Washington School of Medicine.

January 2021