About — Shalem lab

Submitted manuscripts and preprints:

Pooled tagging and hydrophobic targeting of endogenous proteins for unbiased mapping of unfolded protein responses
Stephanie E. Sansbury*, Yevgeniy V. Serebrenik*#, Tomer Lapidot, George M. Burslem and Ophir Shalem#
Provisionally accepted
https://doi.org/10.1101/2023.07.13.548611
Companion website - www.pooledtagging.org

Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins
Jenna N. Beyer, Yevgeniy V. Serebrenik, Kaitlyn Toy, Mohd. Altaf Najar, Nicole R. Raniszewski, Ophir Shalem# and George M. Burslem#
Provisionally accepted
https://doi.org/10.1101/2024.07.08.602493

High-throughput optimized prime editing mediated endogenous protein tagging for pooled imaging of protein localization
Henry M. Sanchez, Tomer Lapidot and Ophir Shalem
Under revision
https://doi.org/10.1101/2024.09.16.613361

CRISPR associated enzymes are mislocalized to the cytoplasm in iPSC-derived neurons resulting in KRAB-specific degradation
Gregory Cajka, Matthew Liu and Ophir Shalem
Under revision
https://doi.org/10.1101/2024.10.19.619045

Selected publication:

CRISPR screen reveals modifiers of rAAV production including known rAAV infection genes playing an unexpected role in vector production
Emily O’Driscoll, Sakshi Arora, Jonathan Lang, Beverly Davidson# and Ophir Shalem#
Molecular Therapy Methods & Clinical Development https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(25)00003-8

Pooled endogenous protein tagging and recruitment for systematic profiling of protein function
Yevgeniy V. Serebrenik, Deepak Mani, Timothé Maujean, George M. Burslem# and Ophir Shalem#
Cell Genomics. https://doi.org/10.1016/j.xgen.2024.100651

Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons
Saranya Santhosh Kumar, Nima N. Naseri, Sarshan R. Pather, Erinc Hallacli, Alain Ndayisaba, Chris Buenaventura, Karen Acosta, Jennifer Roof, Hossein Fazelinia, Lynn A Spruce, Kelvin Luk, Vikram Khurana, Elizabeth Rhoades and Ophir Shalem
Science Advances. https://doi.org/10.1126/sciadv.adj4767

CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly
Katelyn M Sweeney, Sapanna Chantarawong, Edward M Barbieri, Gregory Cajka, Matthew Liu, Lynn Spruce, Hussain Fazelinia, Bede Portz, Katie Copley, Tomer Lapidot, Lauren Duhamel, Phoebe Greenwald, Naseeb Saida, Reut Shalgi, James Shorter and Ophir Shalem
PLoS Genet. 2024 Feb 5;20(2):e1011138. https://doi.org/10.1371/journal.pgen.1011138

Efficient and flexible tagging of endogenous genes by homology-independent intron targeting
Yevgeniy V Serebrenik*, Stephanie E Sansbury*, Saranya Santhosh Kumar, Jorge Henao-Mejia and Ophir Shalem
Genome Res. 2019 Aug;29(8):1322-1328. https://doi.org/10.1101/gr.246413.118

Before Penn:

The Hyaluronidase, TMEM2, Promotes ER Homeostasis and Longevity Independent of the UPRER
Schinzel RT*, Higuchi-Sanabria R*, Shalem O*, Moehle EA, Webster BM, Joe L, Bar-Ziv R, Frankino PA, Durieux J, Pender C, Kelet N, Kumar SS, Savalia N, Chi H, Simic M, Nguyen NT, Dillin A.
Cell. 2019 Nov 27;179(6):1306-1318.e18. https://doi.org/10.1016/j.cell.2019.10.018.

High-throughput functional genomics using CRISPR-Cas9
Shalem O#, Sanjana NE, Zhang F#.
Nat Rev Genet. 2015 May;16(5):299-311. https://doi.org/10.1038/nrg3899

Improved vectors and genome-wide libraries for CRISPR screening
Sanjana NE*, Shalem O*, Zhang F.
Nat Methods. 2014 Aug;11(8):783-784. https://doi.org/10.1038/nmeth.3047

Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem O*, Sanjana NE*, Hartenian E, Shi X, Scott DA, Mikkelson T, Heckl D, Ebert BL, Root DE, Doench JG, Zhang F.
Science. 2014 Jan 3;343(6166):84-87. https://doi.org/10.1126/science.1247005

All publications:

The SMC5/6 complex prevents genotoxicity upon APOBEC3A-mediated replication stress
Fingerman DF, O'Leary DR, Hansen AR, Tran T, Harris BR, DeWeerd RA, Hayer KE, Fan J, Chen E, Tennakoon M, Meroni A, Szeto JH, Devenport J, LaVigne D, Weitzman MD, Shalem O, Bednarski J, Vindigni A, Zhao X, Green AM.
EMBO J. 2024 Aug;43(15):3240-3255. https://doi.org/10.1038/s44318-024-00137

KOLF2.1J iPSCs carry CNVs associated with neurodevelopmental disorders
Gracia-Diaz C, Perdomo JE, Khan ME, Roule T, Disanza BL, Cajka GG, Lei S, Gagne AL, Maguire JA, Shalem O, Bhoj EJ, Ahrens-Nicklas RC, French DL, Goldberg EM, Wang K, Glessner JT, Akizu N.
Cell Stem Cell. 2024 Mar 7;31(3):288-289. https://doi.org/10.1016/j.stem.2024.02.007

A subpopulation of lipogenic brown adipocytes drives thermogenic memory
Lundgren P, Sharma PV, Dohnalová L, Coleman K, Uhr GT, Kircher S, Litichevskiy L, Bahnsen K, Descamps HC, Demetriadou C, Chan J, Chellappa K, Cox TO, Heyman Y, Pather SR, Shoffler C, Petucci C, Shalem O, Raj A, Baur JA, Snyder NW, Wellen KE, Levy M, Seale P, Li M, Thaiss CA.
Nat Metab. 2023 Oct;5(10):1691-1705. https://doi.org/10.1038/s42255-023-00893-w

Impaired ribosome-associated quality control of C9orf72 arginine-rich dipeptide-repeat proteins
Viera Ortiz AP, Cajka G, Olatunji OA, Mikytuck B, Shalem O, Lee EB.
Brain. 2023 Jul 3;146(7):2897-2912. https://doi.org/10.1093/brain/awac479

Large-scale genetic screens identify BET-1 as a cytoskeleton regulator promoting actin function and life span
Garcia G, Bar-Ziv R, Averbukh M, Dasgupta N, Dutta N, Zhang H, Fan W, Moaddeli D, Tsui CK, Castro Torres T, Alcala A, Moehle EA, Hoang S, Shalem O, Adams PD, Thorwald MA, Higuchi-Sanabria R.
Aging Cell. 2023 Jan;22(1):e13742. https://doi.org/10.1111/acel.13742

Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer
Sela Y, Li J, Maheswaran S, Norgard R, Yuan S, Hubbi M, Doepner M, Xu JP, Ho ES, Mesaros C, Sheehan C, Croley G, Muir A, Blair IA, Shalem O, Dang CV, Stanger BZ.
Cancer Res. 2022 May 16;82(10):1890-1908. https://doi.org/10.1158/0008-5472.CAN-22-0431

Cross-species screening platforms identify EPS-8 as a critical link for mitochondrial stress and actin stabilization
Moehle EA, Higuchi-Sanabria R, Tsui CK, Homentcovschi S, Tharp KM, Zhang H, Chi H, Joe L, de Los Rios Rogers M, Sahay A, Kelet N, Benitez C, Bar-Ziv R, Garcia G, Shen K, Frankino PA, Schinzel RT, Shalem O, Dillin A.
Sci Adv. 2021 Oct 29;7(44):eabj6818. https://doi.org/10.1126/sciadv.abj6818

Therapeutic genetic variation revealed in diverse Hsp104 homologs
March ZM, Sweeney K, Kim H, Yan X, Castellano LM, Jackrel ME, Lin J, Chuang E, Gomes E, Willicott CW, Michalska K, Jedrzejczak RP, Joachimiak A, Caldwell KA, Caldwell GA, Shalem O, Shorter J.
Elife. 2020 Dec 15;9:e57457. https://doi.org/10.7554/eLife.57457

Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction
Singh N, Lee YG, Shestova O, Ravikumar P, Hayer KE, Hong SJ, Lu XM, Pajarillo R, Agarwal S, Kuramitsu S, Orlando EJ, Mueller KT, Good CR, Berger SL, Shalem O, Weitzman MD, Frey NV, Maude SL, Grupp SA, June CH, Gill S, Ruella M.
Cancer Discov. 2020 Apr;10(4):552-567. https://doi.org/10.1158/2159-8290.CD-19-0813

Efficient and flexible tagging of endogenous genes by homology-independent intron targeting
Serebrenik YV*, Sansbury SE*, Kumar SS, Henao-Mejia J, Shalem O.
Genome Res. 2019 Aug;29(8):1322-1328. https://doi.org/10.1101/gr.246413.118

CRISPR mutagenesis screening of mice
Serebrenik YV, Shalem O.
Nat Cell Biol. 2018 Nov;20(11):1235-1237. https://doi.org/10.1038/s41556-018-0224-y

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments
Canver MC, Haeussler M, Bauer DE, Orkin SH, Sanjana NE, Shalem O, Yuan GC, Zhang F, Concordet JP, Pinello L.
Nat Protoc. 2018 May;13(5):946-986. https://doi.org/10.1038/nprot.2018.005

Identification of essential genes for cancer immunotherapy
Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK, Cam M, Gartner JJ, Jia L, Steinberg SM, Yamamoto TN, Merchant AS, Mehta GU, Chichura A, Shalem O, Tran E, Eil R, Sukumar M, Guijarro EP, Day CP, Robbins P, Feldman S, Merlino G, Zhang F, Restifo NP.
Nature. 2017 Aug 31;548(7669):537-542. https://doi.org/10.1038/nature23477

CRISPRing the Regulatory Genome, the Challenge Ahead
Sansbury SE, Sweeney KM, Shalem O.
Trends Genet. 2017 Sep;33(9):580-582. https://doi.org/10.1016/j.tig.2017.07.001

Transcription control by the ENL YEATS domain in acute leukaemia
Erb MA, Scott TG, Li BE, Xie H, Paulk J, Seo HS, Souza A, Roberts JM, Dastjerdi S, Buckley DL, Sanjana NE, Shalem O, Nabet B, Zeid R, Offei-Addo NK, Dhe-Paganon S, Zhang F, Orkin SH, Winter GE, Bradner JE.
Nature. 2017 Mar 9;543(7644):270-274. https://doi.org/10.1038/nature21688

High-resolution interrogation of functional elements in the noncoding genome
Sanjana NE, Wright J, Zheng K, Shalem O, Fontanillas P, Joung J, Cheng C, Regev A, Zhang F.
Science. 2016 Sep 30;353(6307):1545-1549. https://doi.org/10.1126/science.aaf7613

Hypoxia as a therapy for mitochondrial disease
Jain IH, Zazzeron L, Goli R, Alexa K, Schatzman-Bone S, Dhillon H, Goldberger O, Peng J, Shalem O, Sanjana NE, Zhang F, Goessling W, Zapol WM, Mootha VK.
Science. 2016 Apr 1;352(6281):54-61. https://doi.org/10.1126/science.aad9642

BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Canver MC, Smith EC, Sher F, Pinello L, Sanjana NE, Shalem O, Chen DD, Schupp PG, Vinjamur DS, Garcia SP, Luc S, Kurita R, Nakamura Y, Fujiwara Y, Maeda T, Yuan GC, Zhang F, Orkin SH, Bauer DE.
Nature. 2015 Nov 12;527(7577):192-7. https://doi.org/10.1038/nature15521

A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks
Parnas O, Jovanovic M, Eisenhaure TM, Herbst RH, Dixit A, Ye CJ, Przybylski D, Platt RJ, Tirosh I, Sanjana NE, Shalem O, Satija R, Raychowdhury R, Mertins P, Carr SA, Zhang F, Hacohen N, Regev A.
Cell. 2015 Jul 30;162(3):675-86. https://doi.org/10.1016/j.cell.2015.06.059

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, Segal E.
PLoS Genet. 2015 Apr 15;11(4):e1005147. https://doi.org/10.1371/journal.pgen.1005147

High-throughput functional genomics using CRISPR-Cas9
Shalem O, Sanjana NE, Zhang F.
Nat Rev Genet. 2015 May;16(5):299-311. https://doi.org/10.1038/nrg3899

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 9;520(7546):186-91. https://doi.org/10.1038/nature14299

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 12;160(6):1246-60. https://doi.org/10.1016/j.cell.2015.02.038

Improved vectors and genome-wide libraries for CRISPR screening
Sanjana NE, Shalem O, Zhang F.
Nat Methods. 2014 Aug;11(8):783-784. https://doi.org/10.1038/nmeth.3047

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;31(9):827-32. https://doi.org/10.1038/nbt.2647

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;9(3):e1002934. https://doi.org/10.1371/journal.pcbi.1002934

Widespread promoter-mediated coordination of transcription and mRNA degradation
Dori-Bachash M*, Shalem O*, Manor YS, Pilpel Y, Tirosh I.
Genome Biol. 2012 Dec 13;13(12):R114. https://doi.org/10.1186/gb-2012-13-12-r114

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 21;31(6):1350-63. https://doi.org/10.1038/emboj.2011.494

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;7(9):e1002273. https://doi.org/10.1371/journal.pgen.1002273

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.
Sci Signal. 2010 Jul 13;3(130):ra53. https://doi.org/10.1126/scisignal.2000952

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;4:223. https://doi.org/10.1038/msb.2008.59