Research Roundup: June 15, 2018

New arrhythmia risk factors, a genetic switch in advanced prostate cancer, and massive-scale drug combination screening at the bench.

Kelly David
Credit: Kelly David

Welcome to the June 15, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Getting to the heart of a dangerous arrhythmia

The largest genetic study of atrial fibrillation (AF) to date sheds new light on the elusive roots of this condition. Reporting in Nature Genetics, a team led by associate member Patrick Ellinor, associate member Steven Lubitz, Carolina Roselli, and Mark D. Chaffin in the Broad Cardiovascular Disease Initiative; and Kathryn Lunetta and Lu-Chen Weng in the Program in Medical and Population Genetics conducted a genome-wide association study involving more than a half-million people from four ethnic groups and found dozens of genetic risk factors for AF, including 67 never before linked to the disorder. Read this Broad news story to learn more about the findings, which the researchers hope will support efforts to develop new drugs to treat AF, or visit the Broad’s Cardiovascular Disease Knowledge Portal to explore the results in several different ways.

Looking beyond genes for prostate cancers' resistance roots

Metastatic prostate cancers react to treatment with vigorous resistance. In a pair of Cell studies, two Broad Cancer Program/Dana-Farber Cancer Institute teams revealed new insights into how. One study, lead by David Takeda, Sandor Spisák, and Broad associate member Matt Freedman, identified a genetic switch, or enhancer, that is active in treatment resistant metastatic cancers, but not localized ones, and which amps up production of a key treatment resistance factor, the androgen receptor (AR). The other, led by Srinivas Viswanathan, Gavin Ha, Andreas Hoff, and institute member Matthew Meyerson, discovered that these cells harbor extra copies of both the enhancer and the AR's gene, as well as widespread changes in genome structure. Learn more in a Broad/Dana-Farber news story.

Searching for antibiotic resistance resistors

One answer to the growing problem of antibiotic resistance is to give antibiotics together with other drugs that could help them enter bacteria more easily or boost their activity. The challenge is finding promising combinations from among the thousands of drugs available. Anthony Kulesa, Jared Kehe, core institute member Paul Blainey, and colleagues have developed a bench-top screening platform that uses optical color-coding and droplet microfluidics to test thousands of drug-antibiotic combinations' antibacterial potential at a time. In PNAS, the team revealed their first findings, gained by screening 10 antibiotics against E. coli in combination with more than 4,000 compounds from the Broad Drug Repurposing Hub. Learn more in this Broad video.

To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.

In this short video, members of the Blainey lab describe their bench-top platform for screening drug-antibiotic combinations that might overcome antibiotic resistance.