For Oliver Rando, being in Tom Maniatis’ Harvard lab when the PI and his team worked out the role of the proteasome in NF-KB activation made the difference between a career in research and one with possibility for direct clinical impact.
Being a member of the lab during its groundbreaking work on NF-KB — the work that led to today’s use of proteasome inhibitors as the frontline treatment for multiple myeloma, Rando says — was the pivotal element in his deciding to get an MD in addition to the PhD he already had in mind.
Now, Rando hangs his hat at the University of Massachusetts Medical School, where he is an assistant professor in the biochemistry and molecular pharmacology department. One of the things that lured Rando, who completed his MD/PhD at Stanford followed by a fellowship at Harvard, was the group of people at UMass — as well as their focus on RNA biology. His enthusiasm for genome-scale technologies, he says, is thanks to work he did in collaboration with Pat Brown at Stanford while he was pursuing his doctoral degrees.
In his lab, chromatin structure is king. Rando uses a number of technologies, including localization studies such as ChIP on chip, to “try to work out what chromatin looks like [and] what role it plays in epigenetic inheritance.” Its role in transcription, which he says has been much better understood in the past five or 10 years, bears further study as well. “Chromatin’s fingers are in a lot of interesting pies,” Rando says.
“The mechanistic question that we’d like to address [is] how nucleosomes move the replication forks, and how old nucleosomes tell new nucleosomes what to look like,” he adds. To that end, his lab collaborates closely with Nir Friedman at Hebrew University. Most of the experimental work — that’s just beginning to focus on mouse embryonic stem cells — is performed at Rando’s lab, while Friedman’s team handles the computational side of it.
And while that’s already resulted in publications and advances in chromatin understanding, Rando says that life would be much improved if there were a way to analyze chromatin structure at the single-cell level. Whether that would be done by microscopy or a cell-sorting approach, he says, “single-cell analysis of chromatin structure — particularly of larger genomic scales — would be revolutionary.”