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News / 06.11.21

Research Roundup: June 11, 2021

Susanna M. Hamilton
Credit : Susanna M. Hamilton
By Broad Communications

A signature of sepsis and COVID-19 outcome; digital data storage in DNA; diet's links to cancer heart disease biology; and more

Welcome to the June 11, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

A marker of infection risk in the elderly

Risk of infection increases dramatically as a person ages, but scientists do not yet fully understand the link between advanced age and immunity. Maryam Zekavat, Shu-Hong Lin, Mitchell Machiela, Giulio Genovese, associate member Pradeep Natarajan of the Medical & Population Genetics Program, and others examined genetic and clinical data from nearly 800,000 patients, finding that those with mosaic chromosomal alterations (mCAs), an acquired rearrangement in blood cell chromosomes, were more likely to develop severe infections such as sepsis, severe COVID-19, and other pneumonias. Screening for mCAs might help identify patients at increased risk for infection who might benefit from preventative measures. Read more in Nature Medicine and a Broad news story.

Connecting CHIP with diet quality

Clonal hematopoiesis of indeterminate potential (CHIP), a condition defined by a set of aging-related genetic mutations in blood cells, is associated with an increased risk of cardiovascular disease. But the inherited risk of developing CHIP is low — so a team led by Romit Bhattacharya, associate member Pradeep Natarajan, and colleagues explored how diet quality may be associated with the prevalence of CHIP as well. Studying UK Biobank data, the researchers observed that an unhealthy diet was independently associated with an increased likelihood of CHIP development and increases in adverse cardiovascular events and death. Find the full story in JAMA Cardiology.

Study of severe COVID-19 sheds light on immune suppression in sepsis

Patients with severe COVID-19 sometimes progress to sepsis, a life-threatening dysfunction of the immune system. A new study led by Miguel Reyes, core institute member Paul Blainey, institute member and Cell Circuits Program co-director Nir Hacohen, and others, including partners at Mass General and Brigham and Women’s Hospital, offers new insight into immune suppression during sepsis. In patients with severe COVID-19, cytokines such as interleukin-6 induce production of a type of blood cell called MS1, which suppresses the immune system, in particular T cells. The work suggests that targeting these cells could one day improve outcomes in many kinds of severe infections. Read more in Science Translational Medicine and a Broad news story.

DNA may be the future of data storage

DNA is better at storing large amounts of digital data, like photos and audio, than most available technologies. However, the current methods to access information from DNA are energetically intensive and lead to data loss over time. James Banal, associate member Mark Bathe in the Stanley Center for Psychiatric Research, and colleagues have developed a fast and energy-efficient way to store and retrieve data from DNA. By encapsulating DNA in barcode-labeled, highly stable silica capsules, they were able to store, physically sort, and randomly access data from DNA with minimal loss. Read more in Nature Materials and an MIT press release.

Tripping an immune alarm against cancer

Therapies called immune checkpoint inhibitors (ICIs), which take the brakes off the immune system, are an attractive therapeutic approach for many forms of cancer. TIM-3, a surface protein found on T cells, is an emerging and potentially important ICI target. Karen Dixon, institute member Vijay Kuchroo of the Klarman Cell Observatory, and colleagues report that deleting TIM-3 from dendritic cells — but not T cells — sparks a strong anti-tumor immune response. They found that TIM-3 controls the activity of inflammasomes (a set of innate immune system sensors); its loss results in increased inflammasome activation and anti-tumor immunity driven by IL-1b and IL-18. Learn more in Nature and a tweetorial by Dixon.

Diet’s effect on intestinal cancer

A study of how diet affects intestinal stem cells in mice has revealed a potential therapeutic target for intestinal cancer. In Cell Reports, Miyeko Mana (now at Arizona State University), associate member Ömer Yilmaz (MIT) in the Infectious Disease and Microbiome Program, and colleagues show that a high-fat diet increased the metabolic activity of intestinal stem cells. This increase, driven by the PPAR nuclear receptor family, led to elevated fatty acid oxidation in the stem cells that promoted tumor development. Inhibition and deletion of a downstream mediator of fatty acid oxidation, CPT1a, lowered stem cell overactivation in mice on high-fat diets, with little effect on mice fed a control diet. This also disrupted tumor growth and metabolism, suggesting a potential therapeutic approach.

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