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Bradley Bernstein: Understanding Embryonic Stem Cells

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Title: Assistant Professor of Pathology, Massachusetts General Hospital

Education: MD, University of Washington, 1999; PhD, University of Washington, 1997

Recommended by: Eric Green

While much of structural genomics can be considered still in its infancy, the study of structures in proteins has a significantly longer track record. Brad Bernstein, an assistant professor of molecular pathology at Mass General, is making strides in understanding genomic structure by relying on his background in structural biology. “In many ways there's a parallel between protein structure and genome structure,” he says. “You're really dealing with a physical entity that is adopting a primary, secondary, and even tertiary structure.”

Bernstein's main interest lies in epigenomics, in which he and his team are using “genomic technologies to obtain global views of epigenetic modifications as they occur across the genome,” he says. In particular, his focus is on how these epigenetic changes play a role in cell identity and cell lineage — which leads his work directly to the intersection of genomics and stem cell research. Not only are epigenetic marks critical to determining whether a cell will turn out to be a liver cell or a skin cell, but recent research indicates that epigenetics may also be at the root of how stem cells stay in their pluripotent state. “You can find signatures of chromatin plasticity [in stem cells] that we think help maintain their ability to turn into almost any different cell type,” he says.

The upshot of all of his research is simple: he hopes one day that all of this will have a positive impact on the landscape of human health. To that end, Bernstein's year-old lab at MGH is just starting to use epigenetic studies in cancer research as well. He posits that a systems-level understanding of chromatin domains and how those domains are regulated and mis-regulated might lead to a better awareness of how epigenetics factors into cancer.

After completing his MD/PhD at the University of Washington, Bernstein fulfilled a “little over a year” of his residency at Brigham & Women's Hospital before becoming a postdoc in Stu Schreiber's lab at Harvard. Bernstein, who currently has affiliations with the Broad Institute, also collaborated with Eric Lander's group during his postdoc.

Looking ahead

There's still technology devel-opment in the offing for Bernstein's field. “We really want to be able to take these tools for profiling the epigenetic state of a cell towards physiologically relevant cells and tissue,” he says. “[But] the technologies aren't quite there yet.” If Bernstein and his team are able to hone their research and tools as they hope to, those studies could play a significant role in oncology, regenerative medicine, and the basic biological understanding of the embryonic stem cell genome, he adds. The ideal tool for the field would give “a single-cell readout of the epigenetic state of a gene — a master regulator gene or critical genomic loci,” says Bernstein. That kind of information would be instrumental not only in identifying stem cell populations but also in obtaining clinically useful diagnostic data about tumor samples, he adds.

Publications of note

In April, Bernstein and his colleagues published a paper in Cell entitled “A bivalent chromatin structure marks key developmental genes in embryonic stem cells.” A year earlier in the same journal, he published another paper explaining how epigenetic and related technologies could help obtain that sort of information.

And the Nobel goes to…

Bernstein says that if a trip to Sweden is in the works for him one day, he’d like to be rehearsing a speech about “gaining another level of understanding of fundamental epigenetic mechanisms in a way that could really translate into having an impact on human health.”

— MWS

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