Engineering and study of protein function by directed evolution has been limited by the
technical requirement to use global mutagenesis or introduce DNA libraries. Here, we develop …

Identification of effective combination therapies is critical to address the emergence of drug-resistant
cancers, but direct screening of all possible drug combinations is infeasible. Here …

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function,
but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely …

The past several years have seen an explosion in development of applications for the
CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment …

The three-dimensional arrangement of the human genome comprises a complex network of
structural and regulatory chromatin loops important for coordinating changes in transcription …

Rare genetic variants are abundant in humans and are expected to contribute to individual
disease risk 1, 2, 3, 4. While genetic association studies have successfully identified common …

2′3′-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator
of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a …

Extracellular 2′3′-cyclic-GMP-AMP (cGAMP) is an immunotransmitter exported by
diseased cells and imported into host cells to activate the innate immune STING pathway. We …

Primary cilia organize Hedgehog signaling and shape embryonic development, and their
dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen …

INTRODUCTION The human genome contains tens of thousands of rare (minor allele frequency
<1%) variants, some of which contribute to disease risk. Using 838 samples with whole-…