Breath-based diagnostics, new cancer biomarkers emerge, more Zika biology revealed, and more
Research Roundup: July 24, 2020
Welcome to the July 24, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Single-cell atlas view of the mouse forebrain
Dysfunction of the thalamic reticular nucleus (TRN) — a gatekeeper for sensory and attention information processing — are implicated in schizophrenia, autism, and attention deficit hyperactivity disorder. However, little is known about its molecular, cellular, and functional organization. By studying the mouse TRN's molecular and electrophysiological features at the single-cell level, Yinqing Li, Violeta Lopez-Huerta, research scientist Xian Adiconis, senior group leader Joshua Levin, associate director of neurophysiology Zhanyan Fu, and institute member Guoping Feng of the Stanley Center for Psychiatric Research, and colleagues have produced a comprehensive atlas of TRN neurons and linked genetic subnetworks within it to the functional organization of the mammalian forebrain. Learn more in Nature and MIT News.
Breath test to diagnose disease
Human breath contains many volatile metabolites, but breath tests are not widely used in the clinic because of difficulties in biomarker detection. Using specialized nanoparticles, institute member Sangeeta Bhatia and colleagues have developed a strategy for monitoring respiratory disease biomarkers in exhaled breath. The researchers reported in Nature Nanotechnology that they could use this system in mice to monitor bacterial pneumonia and alpha-1 antitrypsin deficiency, a genetic lung disorder. Learn more in MIT News.
Casting a wide net for cancer biomarkers
The development of patient-specific cancer therapies requires predictive biomarkers. A team led by Rotem Ben-Hamo and institute member Gad Getz in the Cancer Program and Ravid Straussman (Weizmann Institute) developed a method for selecting the best therapy for a given tumor based on the cells’ internal signaling pathways. The researchers integrated gene expression and drug sensitivity datasets on hundreds of anti-cancer drugs across 460 cancer cell lines from 10 tissue types. The study revealed dozens of predictive biomarkers and suggested that larger datasets could uncover even more in the future. Read more in Nature Communications and a Weizmann Institute press release.
Watching tumors reimagine themselves
Cancer cells are hardly static; indeed, they tend to evolve dramatically over time. In complementary studies published in Cancer Cell, two Broad-led teams profiled mouse lung cancer models to understand tumor cell states and how they track with progression and prognosis. In one study, Lindsay LaFave (MIT), Sai Ma, core institute member and Klarman Cell Observatory director Aviv Regev, associate members Jason Buenrostro and Tyler Jacks, and collaborators used single-cell epigenomics to examine how cancer cells regulate transitions between states. In the other, Nemanja Despot Marjanovic, Matan Hofree, Jason Chan (MSKCC), Jacks, Regev, Tuomas Tammela (MSKCC), and colleagues used single-cell RNA-sequencing to reveal a new state through which tumor cells can evolve into a wide variety of subtypes.
A buzz kill for Zika
In the search for host factors involved in Zika virus replication, a team led by Federico Giovannoni (Brigham and Women’s), Jean Pierre Schatzmann Peron (University of São Paulo), Cybele Garcia (Universidad de Buenos Aires), and associate member Francisco Quintana of the Metabolomics Platform and Brigham and Women’s Hospital performed genome-wide transcriptional studies of infected cells. Reporting in Nature Neuroscience, they found that Zika triggers activation of the aryl hydrocarbon receptor (AHR), which reduces type I interferon levels. AHR inhibition suppressed replication of both Zika and the related dengue virus in vitro, and in an animal model prevented Zika-induced newborn microcephaly.