Ophir Shalem, Ph.D.

Visiting Scholar

Research

Since January 2013 I have been working as a postdoctoral research associate at the lab of Prof. Feng Zhang, located at the Broad institute of MIT and Harvard. On October 2014 I joined the Dillin lab as a visiting scholar.

I completed my PhD training at the Weizmann Institute of Science working under the supervision of Prof. Tzachi Pilpel and Prof. Eran Segal. During my PhD I studied gene expression regulation and RNA metabolism and contributed to the understanding of how different regulatory layers are coordinated to produce concise temporal expression patterns. Before that I received by bachelor’s degree in computer science and biology from Ben Gurion University.

During my postdoc at the Zhang lab we pioneered the use of pooled CRISPR libraries for functional knockout screening in mammalian cells. In my current work I combine technology development of large scale perturbation screens with the application of such technology to the study of proteotoxic stress responses and their malfunction in neurodegenerative diseases. I am developing models to study this in human cell lines, stem cell derived cells and mouse primary cells with the aim of understanding the effect of aging and genetic variability on these networks.

I am supported by a fellowship funded by the Klarman Family Foundation.

Publications

Systematic dissection of the sequence determinants of gene 3’ end mediated expression control.
Shalem O*, Sharon E*, Lubliner S, Regev I, Lotan-Pompan M, Yakhini Z and Segal E. PLoS Genet. 2015 June

High-throughput functional genomics using CRISPR-Cas9.
Shalem O‡, Sanjana NE and Zhang F‡. Nature Rev Genet. 2015 Apr (‡ corresponding authors)

In vivo genome editing using Staphylococcus aureus Cas9.
Ran FA*, Cong L*, Yan WX*, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. Nature 2015 Apr

Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis.
Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA. Cell 2015 Mar

Improved lentiviral vectors and genome-wide libraries for genetic screening in human and mouse cells using the CRISPR nuclease Cas9.
Sanjana NE*, Shalem O* and Zhang F. Nature Methods. 2014 Aug

Genome-scale CRISPR-Cas9 knockout screening in human cells.
Shalem O*, Sanjana NE*, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG, Zhang F. Science 2014 Jan (Science research highlightsNature research highlightsNature Genetics research highlightsNature Methods research highlights)

DNA targeting specificity of RNA-guided Cas9 nucleases.
Hsu PD*, Scott DA*, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, Cradick TJ, Marraffini LA, Bao G, Zhang F. Nat Biotechnol. 2013 Sep

Measurements of the impact of 3′ end sequences on gene expression reveal wide range and sequence dependent effects.
Shalem O, Carey L, Zeevi D, Sharon E, Keren L, Weinberger A, Dahan O, Pilpel Y, Segal E. PLoS Comput Biol. 2013

Widespread promoter-mediated coordination of transcription and mRNA degradation.
Dori-Bachash M*, Shalem O*, Manor YS, Pilpel Y, Tirosh I. Genome Biol. 2012 Dec

Axonal transcription factors signal retrogradely in lesioned peripheral nerve.
Ben-Yaakov K, Dagan SY, Segal-Ruder Y, Shalem O, Vuppalanchi D, Willis DE, Yudin D, Rishal I, Rother F, Bader M, Blesch A, Pilpel Y, Twiss JL, Fainzilber M. EMBO J 2012 Mar

Transcriptome kinetics is governed by a genome-wide coupling of mRNA production and degradation: a role for RNA Pol II.
Shalem O, Groisman B, Choder M, Dahan O, Pilpel Y. PLoS Genet. 2011 Sep

Signaling to transcription networks in the neuronal retrograde injury response.
Michaelevski I, Segal-Ruder Y, Rozenbaum M, Medzihradszky KF, Shalem O, Coppola G, Horn-Saban S, Ben-Yaakov K, Dagan SY, Rishal I, Geschwind DH, Pilpel Y, Burlingame AL, Fainzilber M.
Science Signal. 2010 Jul 13

Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation.
Shalem O, Dahan O, Levo M, Martinez MR, Furman I, Segal E, Pilpel Y. Mol Syst Biol. 2008 (F1000 review)