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News / 05.17.19

Research Roundup: May 17, 2019

Erik Jacobs
Credit : Erik Jacobs
By Broad Communications

Helping insulin stick around, barcodes for development tracking, and a promising leukemia drug clears the first gate.

Welcome to the May 17, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Reprogramming enzymes with small molecules

One potential way to treat diabetes is to keep insulin around longer by preventing its degradation. Core institute member and Merkin Institute for Transformative Technologies in Healthcare director David Liu and others previously discovered inhibitors of insulin-degrading enzyme (IDE) that could help control blood glucose levels. Because IDE also degrades the insulin-regulating hormone, glucagon, an ideal IDE inhibitor would help insulin linger while letting IDE break down glucagon. In Nature Chemical Biology, Liu and Juan Pablo Maianti, along with Grace Tan and Markus Seeliger (Stony Brook University) and colleagues, describe a new class of drug-like small-molecule IDE inhibitors that block IDE’s effect on insulin but not other hormones, demonstrating how enzyme substrate specificity can be reprogrammed with small molecules as a new therapeutic strategy.

Tracing development, cell by cell

Mammalian development, from a single fertilized cell to a fully grown organism, is an extremely complex process. In Nature, a team led by Zachary Smith, Epigenomics Program associate member Alexander Meissner, and colleagues reports a new tool to track cell differentiation starting from a fertilized egg. The tool uses CRISPR-Cas9 to introduce random mutations in a synthetic piece of DNA, allowing new cells to be "barcoded" by their unique mutation patterns as they divide. The development of an organism grown from a barcoded egg can then be mapped by single-cell sequencing. The team validated their tool by analyzing cell and tissue development in mice. Learn more in a news release from the Max Planck Institute for Molecular Genetics.

A Broad-fueled trial shows promise

A pilot Phase 1 clinical trial based on research involving the Broad's Proteomics Platform, former RNAi Platform (now the Genetic Perturbation Platform) and Chemical Biology Program (now the Chemical Biology and Therapeutics Science Program), and Imaging Platform has reported positive results. In 2012, a team led by Broad and Northwestern University researchers homed in on aurora A kinase (AURKA) as a therapeutic target in acute megakaryoblastic leukemia, a rare cancer. This new trial, conducted by a Northwestern-led team and reported in Clinical Cancer Research, showed that an AURKA-blocking compound called alisertib was safe and had clinical benefit in patients with myelofibrosis, a closely related condition.

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