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Rational design of highly active sgRNAs for CRISPR-Cas9–mediated gene inactivation
Components of the prokaryotic clustered, regularly interspaced, short palindromic repeats (CRISPR) loci have recently been repurposed for use in mammalian cells. The CRISPR-associated (Cas)9 can beExpand
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CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockinExpand
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From genetics of inflammatory bowel disease towards mechanistic insights.
Advancements in human genetics now poise the field to illuminate the pathophysiology of complex genetic disease. In particular, genome-wide association studies (GWAS) have generated insights into theExpand
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Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo.
Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models of disease has beenExpand
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Resources for the design of CRISPR gene editing experiments
CRISPR-based approaches have quickly become a favored method to perturb genes to uncover their functions. Here, we review the key considerations in the design of genome editing experiments, andExpand
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Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, weExpand
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Therapeutic Opportunities in Inflammatory Bowel Disease: Mechanistic Dissection of Host-Microbiome Relationships
The current understanding of inflammatory bowel disease (IBD) pathogenesis implicates a complex interaction between host genetics, host immunity, microbiome, and environmental exposures. MechanismsExpand
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Protein kinase C–delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts
Bone homeostasis requires stringent regulation of osteoclasts, which secrete proteolytic enzymes to degrade the bone matrix. Despite recent progress in understanding how bone resorption occurs, theExpand
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Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.
Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentiallyExpand
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Small-molecule inhibitors directly target CARD9 and mimic its protective variant in inflammatory bowel disease
Significance Understanding the genetic basis of human disease can reveal mechanisms of disease pathology and guide the design of novel treatment strategies. Here, we leverage insights from geneticExpand
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