Research Roundup: April 5, 2019

Breaking blood diseases, distinguishing wolves, quantifying prions, and more.

Erik Jacobs
Credit: Erik Jacobs

Welcome to the April 5, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Blocking BCL11A brings better blood

In Nature Medicine, Yuxuan Wu, Jing Zeng, and associate member Daniel Bauer describe a new approach to edit genes in blood stem cells. Using CRISPR-Cas9 to target a genetic enhancer of the BCL11A gene, their protocol edited to near completion blood stem cells they collected from patients with sickle cell disease and beta-thalassemia. In mice, the cells engrafted in the bone marrow and produced genetically corrected red blood cells that produced functional hemoglobin. The work demonstrates that targeting the BCL11A enhancer could represent a potent therapeutic approach for hemoglobin disorders. Read more on Boston Children’s Hospital’s Vector blog.

Both of these wolves are not like the others

Taxonomic classifications are essential for identifying populations to be listed under the Endangered Species Act. The Program in Medical and Population Genetics' Diane Genereux and colleagues recently took part in a National Academy of Science (NAS) study reviewing the taxonomy of the red wolf and the Mexican gray wolf, two species that nearly became extinct in the 1900s but are rebounding thanks to conservation efforts. Considering the available genetic, morphologic, and behavioral data, the team concluded that the modern red wolf is a distinct species, while the Mexican gray wolf is a distinct subspecies of the gray wolf found throughout North America. Learn more in an NAS press release.

Quantifying prion protein to cure prion disease

Prion disease is a fatal neurodegenerative disease caused by misfolding of the prion protein (PrP), and  reducing PrP levels in the brain may be a therapeutic strategy. However, clinical development of a PrP-reducing drug will require an appropriate biomarker which can accurately quantify PrP levels in the brains of living patients. A team led by Sonia Vallabh, Eric Vallabh Minikel, and core institute member Stuart Schreiber in the Chemical Biology and Therapeutics Science Program used ELISA, a method to measure proteins, to quantify levels of PrP in 225 human cerebrospinal fluid (CSF) samples. Reporting in PNAS, the team confirms that quantifying PrP levels in CSF samples will be a suitable biomarker for clinical trials of PrP-lowering drugs. Read more in GenomeWeb.

Charting the course for DepMap

A piece by the Broad Cancer Program's Yuen-Yi (Moony) Tseng and Jesse Boehm recently published in Current Opinion in Genetics & Development, described how the team is using living tumor material to generate a functional map of cancer dependencies – the Cancer Dependency Map, or DepMap. Specifically, they highlight how the large-scale profiling of long-term, ex vivo cell models; the growing viability of short-term, patient-derived cell models; and the increasing feasibility of “alpha cancer cultures” profiled just hours after patient sampling are making it possible for functional genomics information from nearly every patient’s tumor to contribute to DepMap and improve precision medicine predictions for future patients.

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