Ophir Shalem, Ph.D.

Assistant Professor of Genetics
Department: Genetics
Graduate Group Affiliations
Contact information
5050 Colket Translational Research Building
3501 Civic Center Boulevard
Philadelphia, PA 19104
3501 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215-590-4168
Email:
shalemo@upenn.edu
shalemo@upenn.edu
Publications
Education:
B.Sc. (Computer Science and Biology, Bioinformatics Track in the Computer Science Department)
Ben Gurion University of The Negev, Beer Sheva, Israel, 2004.
M.Sc. (Bioinformatics, Advisors: Tzachi Pilpel and Eran Segal)
The Weizmann Institue of Science, 2007.
Ph.D. (Biology and Computer Science, Advisors: Tzachi Pilpel and Eran Segal)
The Weizmann Institue of Science, 2012.
Permanent linkB.Sc. (Computer Science and Biology, Bioinformatics Track in the Computer Science Department)
Ben Gurion University of The Negev, Beer Sheva, Israel, 2004.
M.Sc. (Bioinformatics, Advisors: Tzachi Pilpel and Eran Segal)
The Weizmann Institue of Science, 2007.
Ph.D. (Biology and Computer Science, Advisors: Tzachi Pilpel and Eran Segal)
The Weizmann Institue of Science, 2012.
Description of Research Expertise
Our lab is interested in functional genomics, approaches that are aimed at understanding gene function by following the effects of direct perturbations at a large scale, we are developing novel perturbation and functional genomics approaches and applying them together with additional genomics approaches to study a range of human diseases including early and late onset neurodegenerative diseases.Selected Publications
O’Driscoll E*, Arora S*, Lang J, Davidson B# and Shalem O#: CRISPR screen reveals modifiers of rAAV production including known rAAV infection genes playing an unexpected role in vector production. Molecular Therapy Methods & Clinical Development Feb 2025 Notes: https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(25)00003-8.Sansbury SE, Serebrenik YV, Lapidot T, Burslem GM, Shalem O.: Pooled tagging and hydrophobic targeting of endogenous proteins for unbiased mapping of unfolded protein responses. Molecular Cell (provisionaly accepted) 2025.
Jenna N Beyer, Yevgeniy V Serebrenik, Kaitlyn Toy, Mohd Altaf Najar, Nicole R Raniszewski, Ophir Shalem#, George M Burslem#: Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins. Science (provisionally accepted) 2025.
Gregory Cajka, Matthew Liu and Ophir Shalem: CRISPR associated enzymes are mislocalized to the cytoplasm in iPSC-derived neurons resulting in KRAB-specific degradation. bioRxiv Oct 2024 Notes: under review, Cell Systems.
Serebrenik YV, Mani D, Maujean T, Burslem GM, Shalem O.: Pooled endogenous protein tagging and recruitment for scalable discovery of effectors for induced proximity therapeutics. Cell Genomics Sep 2024.
Sanchez H, Lapidot T and Shalem O: High-throughput optimized prime editing mediated endogenous protein tagging for pooled imaging of protein localization. bioRxiv Sep 2024 Notes: Nature Cell Biology, under revision.
Dylan F Fingerman, David R O'Leary, Ava R Hansen, Thi Tran, Brooke R Harris, Rachel A DeWeerd, Katharina E Hayer, Jiayi Fan, Emily Chen, Mithila Tennakoon, Alice Meroni, Julia H Szeto, Jessica Devenport, Danielle LaVigne, Matthew D Weitzman, Ophir Shalem, Jeffrey Bednarski, Alessandro Vindigni, Xiaolan Zhao, Abby M Green : The SMC5/6 complex prevents genotoxicity upon APOBEC3A-mediated replication stress. EMBO J 43(15): 3240-3255, Aug 2024.
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.: KOLF2.1J iPSCs carry CNVs associated with neurodevelopmental disorders. Cell Stem Cell 31(3): 288-289, Mar 2024 Notes: My lab have been using the KOLF2.1J iPSC lines extensively, we were involved in the initial genotyping efforts that resulted in this finding which was then further validated and deeply characterized by the Akizu lab.
Sweeney KM, Chantarawong S, Barbieri EM, Cajka G, Liu M, Spruce L, Fazelinia H, Portz B, Copley K, Lapidot T, Duhamel L, Greenwald P, Saida N, Shalgi R, Shorter J, Shalem O.: CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly. PLoS Genet 20(2): e1011138, Feb 2024.
Santhosh Kumar S, Naseri NN, Pather SR, Hallacli E, Ndayisaba A, Buenaventura C, Acosta K, Roof J, Fazelinia H, Spruce LA, Luk K, Khurana V, Rhoades E, Shalem O.: Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. Sci Adv 10(6): eadj4767, Feb 2024.