Ophir Shalem
Broad Institute
Publications 39
#1Matthew C. Canver (Harvard University)H-Index: 13
Last.Luca Pinello (Harvard University)H-Index: 20
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This protocol describes how to set up arrayed and pooled CRISPR genome-editing experiments. It describes the design of sgRNAs using CRISPOR, the wet-lab implementations, and analysis of the generated results by CRISPResso.
#1Shashank J. PatelH-Index: 11
#2Neville E. SanjanaH-Index: 21
Last.Tori N. YamamotoH-Index: 12
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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.
#1Michael A. ErbH-Index: 7
#2Thomas G. ScottH-Index: 7
Last.Dennis L. BuckleyH-Index: 14
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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.
#1Neville E. Sanjana (Broad Institute)H-Index: 21
#2Jason Wright (Broad Institute)H-Index: 7
Last.Feng Zhang (Broad Institute)H-Index: 104
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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...
#1Isha H. JainH-Index: 6
#2L. ZazzeronH-Index: 9
Last.Warren M. ZapolH-Index: 70
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#1Isha H. Jain (Broad Institute)H-Index: 6
#2L. Zazzeron (Harvard University)H-Index: 9
Last.Neville E. Sanjana (MIT: Massachusetts Institute of Technology)H-Index: 21
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Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured c...
#1Daniel E. Bauer (Harvard University)H-Index: 32
#2Matthew C. Canver (Harvard University)H-Index: 13
Last.Divya S. Vinjamur (Harvard University)H-Index: 3
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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...
#1Matthew C. Canver (Harvard University)H-Index: 13
#2Elenoe C. Smith (Harvard University)H-Index: 6
Last.Sara P. Garcia (Harvard University)H-Index: 6
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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...
#1Yiguo Hu (Harvard University)H-Index: 15
#2Michal Sheffer (Harvard University)H-Index: 12
Last.B. Aftab (Harvard University)
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OP-001 A Meta-Analysis Investigating the Impact of Minimal Residual Disease (MRD) Status on Survival Outcomes in Patients With Multiple Myeloma (MM) who Achieve Complete Response (CR) N. Munshi, H. Avet-Loiseau, A. Rawstron, R. Owen, A. Thakurta, P. Sherrington, A. Georgieva, K. Anderson, W. Gregory Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Unit for Genomics in Myeloma, Institut Universitaire du Cancer, Toulouse, France; St James’s University Hospital, Leeds, United ...