Relationships explored: between lifespan and selenium, between driver genes and leukemia growth, between the microbiome and IBD, and more.
Research Roundup: May 31, 2019
Welcome to the May 31, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
The (Se)eds of a long life
Too much, or too little, of the essential trace element selenium (Se) can be a health risk. A new study led by Broad Metabolism Program associate member Vadim Gladyshev, institute scientist and Metabolomics Platform senior director Clary Clish, and Metabolomics Platform associated scientist Sun Hee Yim took a combination of -omics approaches to study how dietary Se regulates metabolism at the molecular level and how it affects lifespan in mice. Appearing in Cell Reports, their work revealed that Se deficiency reduces selenoprotein expression, but not lifespan, and is associated with pro-longevity mechanisms related to reduced amino acid levels and altered nutrient signaling. Future study could reveal how dietary Se deficiency may work to increase lifespan.
Directing cancer progression
The impact of genomic features on a cancer’s progression in patients is not yet fully understood. A team led by Ivana Bozic of the University of Washington and Michaela Gruber, Ignaty Leshchiner, Dimitri Livitz, institute member Gad Getz, and institute member Catherine Wu of the Broad Cancer Program has now characterized the growth dynamics of chronic lymphocytic leukemia, and reports that the cancer’s growth rate is tightly linked to the cells’ genetics, particularly the number of growth-spurring “driver” mutations. Genetic changes that occur very early in disease development further influence the growth pattern. Check out the full story in Nature and a news release from Dana-Farber Cancer Institute.
Cancer drug resistance opens a metabolic back door
Drugs that block the proteasome — the cell’s protein recycling machine — are often initially successful at treating some forms of cancer, but over time, patients tend to develop resistance. In this week's Nature Chemical Biology, Peter Tsvetkov, core institute member and Cancer Program director Todd Golub, and colleagues traced the roots of proteasome inhibitor resistance to a fundamental shift in cancer cells’ metabolism. This shift creates a metabolic dependency that the researchers exploited with a drug called elesclomol, which they found interferes with a key mitochondrial enzyme and triggers a unique form of copper-driven cell death. Learn more in news stories from Broad and the Whitehead Institute.
IBD’s toll on the microbiome
A new study appearing in Nature, is the first to observe the complex set of chemical and molecular events that disrupt the gut microbiome and trigger immune responses during inflammatory bowel diseases (IBD). The researchers, led by associate member Curtis Huttenhower and core institute member and Infectious Disease and Microbiome Program co-director Ramnik Xavier, developed a unique biotechnology toolbox to understand why microbiomes change during IBD and how this provokes an unhealthy inflammatory reaction and could reveal future treatment opportunities. The study was part of the second phase of the Human Microbiome Project. Read more in a Broad news story or on the NIH blog.