Pancreatic ductal adenocarcinoma is an aggressive and lethal cancer, with a five-year survival rate of only 13%.

Our research focuses on understanding the mechanisms driving pancreatic cancer progression. We aim to identify key molecular regulators that can be targeted to inhibit primary tumor growth and to elucidate the processes involved in metastatic seeding and formation.

In parallel, we conduct CRISPR/Cas9 screens to identify genes in immune cells that mediate responses to immunosuppressive signals. Targeting these genes holds the potential to enhance the immune system’s ability to combat cancer. We have discovered gene combinations in dendritic cells that improve T-cell priming and are now extending this approach to engineer additional immune cell types for more effective cancer immunotherapy.

1. Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation. Xia L*, Komissarova A*, Jacover A*, Shovman Y*, Arcila-Barrera S, Tornovsky-Babeay S, Jaya-Prakashan MM, Nasereddin A, Plaschkes I, Nevo Y, Shiff I, Yosefov-Levi O, Izhiman T, Medvedev E, Eilon E, Wilensky A, Yona S, Parnas O. Nature Communications, 2023 Oct 9;14(1):6295.

2. It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease. Cephas AT, Hwang WL, Maitra A, Parnas O, DelGiorno KE. Gut. 2023 Jun;72(6):1211-1219.

3. Targeting the Kaposi’s sarcoma-associated herpesvirus genome with the CRISPR-Cas9 platform in latently infected cells. Haddad CO, Kalt I, Shovman Y, Xia L, Schlesinger Y, Sarid R, Parnas O. Virol J. 2021 Mar 17;18(1):56.

4. Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity. Schlesinger Y, Yosefov-Levi O, Kolodkin-Gal D, Granit RZ, Peters L, Kalifa R, Xia L, Nasereddin A, Shiff I, Amran O, Nevo Y, Elgavish S, Atlan K, Zamir G, Parnas O. Nature Communications. 2020 Sep 9;11(1):4516.

5. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Dixit A*, Parnas O*, Li B, Chen J, Fulco CP, Jerby-Arnon L, Marjanovic ND, Dionne D, Burks T, Raychowdhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, Regev A. Cell. 2016 Dec 15;167(7):1853-1866.

6. 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.
   
   

7. Shemesh k, Sebesta M, Pacesa M, Sau S, Parnas O, Bronstein A, Liefshitz B, Venclovas C, Krejci L, Kupiec Martin.
   A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance. Nucleic Acids Res. 2017 Jan 20.

8. Dixit A*, Parnas O*, Li B, Chen J, Fulco CP, Jerby L, Marjanovic ND, Dionne D, Burks T, Raychndhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, Regev A. Perturb-seq: Dissecting molecular circuits with scalable single cell RNA profiling of pooled genetic screens. Cell. 2016 Dec 15;167(7):1853-1866.

9. Adamson B, Norman TM, Jost M, Cho MY, Nuñez JK, Chen Y, Villalta JE, Gilbert LA, Horlbeck MA, Hein MY, Pak RA, Gray AN, Gross CA, Dixit A, Parnas O, Regev A, Weissman JS. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell. 2016 Dec 15;167(7):1867-1882.

10. Lee J, Moraes-Vieira PM, Castoldi A, Aryal P, Yee EU, Vickers C, Parnas O, Donaldson CJ, Saghatelian A, Kahn BB. Branched fatty acid esters of hydroxy fatty acids (FAHFAs) protect against colitis by regulating the gut innate and adaptive immune systems. J Biol Chem. 2016 Oct 14;291(42):22207-22217

11. Parnas O*, Jovanovic M*, Eisenhaure TM*, Herbst RH, Dixit A, Ye C, Przybylski D, Platt RJ, Tirosh I, Sanjana NE, Shalem O, Satija R, Raychowdhury R, Mertins P, Carr SA, Zhang F, Hacohen N, Regev A. A genome-wide CRISPR screen in primary immune cells to dissect regulatory networks. 2015. Cell. 2015 Jul 30;162(3):675-86.

12. Gazy I, Liefshitz B, Parnas O, Kupiec M. Elg1, a central player in genome stability. Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:267-79. Review.

13. Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell. 2014 Oct 9;159(2):440-55.

14. Parnas O, Corcoran DL, Cullen BR. Analysis of the mRNA targetome of microRNAs expressed by Marek’s disease virus. MBio. 2014 Jan 21;5(1):e01060-13.

15. Gazy I, Liefshitz B, Bronstein A, Parnas O, Atias N, Sharan R and Kupiec M. A genetic screen for high-copy-number suppressors of the synthetic lethality between elg1 and srs2 in yeast. G3 (Bethesda). 2013 May 20;3(5):917-26.

16. Parnas O, Amishay R, Liefshitz B, Zipin-Roitman A and Kupiec, M. Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins. Cell Cycle. 2011 Sep 1;10(17).

17. Parnas O, Kupiec M. Establishment of sister chromatid cohesion: the role of the clamp loaders. Views & News Cell Cycle. 2010 Dec 1;9(23):4615.

18. Parnas O, Zipin-Roitman A, Pfander B, Liefshitz B, Mazor Y, Ben-Aroya S Jentsch S and Kupiec M. Elg1, an alternative subunit of the RFC clamp loader, is specific for SUMOylated PCNA. EMBO Journal. 2010 Aug 4;29(15):2611-22.

19. Parnas O, Zipin-Roitman A, Mazor Y, Liefshitz B, Ben-Aroya S, Kupiec M. The ELG1 clamp loader plays a role in sister chromatid cohesion. PLoS ONE. 2009;4(5):e5497.