Ophir Shalem
Broad Institute
38Publications
18H-index
7,598Citations
Publications 38
Newest
Published on Mar 1, 2017in Nature 41.58
Michael A. Erb7
Estimated H-index: 7
,
Thomas G. Scott7
Estimated H-index: 7
+ 17 AuthorsJames E. Bradner71
Estimated H-index: 71
ENL, identified in a genome-scale loss-of-function screen as a crucial requirement for proliferation of acute leukaemia, is required for leukaemic gene expression, and its YEATS chromatin-reader domain is essential for leukaemic growth.
45 Citations Source Cite
Published on Aug 1, 2017in Nature 41.58
Shashank J. Patel10
Estimated H-index: 10
,
Neville E. Sanjana20
Estimated H-index: 20
+ 21 AuthorsTori N. Yamamoto12
Estimated H-index: 12
The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function.
114 Citations Source Cite
Published on Sep 30, 2016in Science 41.06
Neville E. Sanjana20
Estimated H-index: 20
(Broad Institute),
Jason Wright7
Estimated H-index: 7
(Broad Institute)
+ 6 AuthorsFeng Zhang101
Estimated H-index: 101
(Broad Institute)
The noncoding genome affects gene regulation and disease, yet we lack tools for rapid identification and manipulation of noncoding elements. We developed a CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes NF1 , NF2 , and CUL3 , which are involved in BRAF inhibitor resistance in melanoma. We find that noncoding locations that modulate drug resistance also harbor predictive hallmarks of noncoding function. With a subset of regions at the CUL3 locus, we d...
92 Citations Source Cite
Published on Jul 1, 2015in Cell 31.40
Oren Parnas5
Estimated H-index: 5
(Broad Institute),
Marko Jovanovic12
Estimated H-index: 12
(Broad Institute)
+ 15 AuthorsNeville E. Sanjana20
Estimated H-index: 20
Summary Finding the components of cellular circuits and determining their functions systematically remains a major challenge in mammalian cells. Here, we introduced genome-wide pooled CRISPR-Cas9 libraries into dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (Tnf) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the Tlr4 pathway. We found many of the known regulators of Tlr4 signaling, as well as dozen...
192 Citations Source Cite
Published on Mar 1, 2015in Cell 31.40
Sidi Chen17
Estimated H-index: 17
(Massachusetts Institute of Technology),
Neville E. Sanjana20
Estimated H-index: 20
+ 10 AuthorsRalph Weissleder151
Estimated H-index: 151
(Harvard University)
Summary Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were ...
286 Citations Source Cite
Published on Nov 1, 2015in Nature 41.58
Matthew C. Canver12
Estimated H-index: 12
(Harvard University),
Elenoe C. Smith6
Estimated H-index: 6
(Harvard University)
+ 16 AuthorsSara P. Garcia4
Estimated H-index: 4
(Harvard University)
Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered...
282 Citations Source Cite
Published on Dec 3, 2015in Blood 15.13
Daniel E. Bauer31
Estimated H-index: 31
(Harvard University),
Matthew C. Canver12
Estimated H-index: 12
(Harvard University)
+ 17 AuthorsDivya S. Vinjamur3
Estimated H-index: 3
(Harvard University)
Common genetic variation associated with fetal hemoglobin (HbF) level and β-hemoglobin disorder clinical severity marks an erythroid enhancer within the BCL11A gene. The 12 kb intronic enhancer contains three ~1 kb erythroid DNase I hypersensitive sites (DHSs), termed +55, +58, and +62. Here we utilized a human adult-stage erythroid cell line to show by CRISPR-Cas9 mediated targeted deletion that the composite enhancer is required both for BCL11A expression and HbF repression. Because deletion o...
4 Citations
Published on Apr 1, 2015in Nature 41.58
F. Ann Ran10
Estimated H-index: 10
,
Le Cong15
Estimated H-index: 15
+ 10 AuthorsKira S. Makarova76
Estimated H-index: 76
The physical size of the commonly used Cas9 from Streptococcus pyogenes poses challenges for CRISPR-Cas genome editing systems that use the adeno-associated virus as a delivery vehicle; here, smaller Cas9 orthologues are characterized, and Cas9 from Staphylococcus aureus allowed targeting of the cholesterol regulatory gene Pcsk9 in the mouse liver.
843 Citations Source Cite
Published on Apr 15, 2015in PLOS Genetics 5.54
Ophir Shalem18
Estimated H-index: 18
(Weizmann Institute of Science),
Eilon Sharon13
Estimated H-index: 13
(Weizmann Institute of Science)
+ 4 AuthorsEran Segal66
Estimated H-index: 66
(Weizmann Institute of Science)
The 3’end genomic region encodes a wide range of regulatory process including mRNA stability, 3’ end processing and translation. Here, we systematically investigate the sequence determinants of 3’ end mediated expression control by measuring the effect of 13,000 designed 3’ end sequence variants on constitutive expression levels in yeast. By including a high resolution scanning mutagenesis of more than 200 native 3’ end sequences in this designed set, we found that most mutations had only a mild...
22 Citations Source Cite
Published on May 1, 2015in Nature Reviews Genetics 41.47
Ophir Shalem18
Estimated H-index: 18
,
Neville E. Sanjana20
Estimated H-index: 20
,
Feng Zhang101
Estimated H-index: 101
CRISPR–Cas9 has been adopted as a powerful genome-editing technology in various species. By generating libraries of thousands of guide RNAs — which direct the Cas9 nuclease to chosen genomic loci — high-throughput genetic perturbations are now possible. This Review discusses the latest applications of CRISPR–Cas9 in mammalian functional genomics screens. It covers related genome-scale applications of Cas9 for either gene knockout or transcriptional modulation, and provides comparisons with compl...
408 Citations Source Cite
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