The interactions between the immune system and cancer.
The Parnas lab goal is to explore the effect of suppressive signals on innate immune cells, especially dendritic cells. We focus on suppressive signals that produced by cancer. Cancer escapes the immune system using several strategies including the production of signals that suppress the ability of the immune system to respond to danger. We explore:
(1) Which suppressive signals produce by cancer? At which stage during the development of the disease, and how they affect the immune cells.
(2) Which key genes, that expressed by immune cells, sense and transfer the suppressive signals and therefore can be targeted to block the effect of the suppressive signals.
We are using advanced genetics and genomics methods, to characterize the interactions between the immune cells and the malignant cells in ovarian cancer mouse model. It includes single cell RNA-Seq technics that enables to monitor cell type and cell state in an unbiased way and genome wide CRISPR-CAS9 screens that are useful in order to find new genes that play a role in immune regulation. We hypothesize that targeting those genes can reverse the dysfunction phenotype of the immune system in advance cancer and restore the immune system ability to fight cancer. We have already found several new genes that play a role in immune suppression and we are investigating their regulation and exploring their molecular mechanism.
In addition, we investigate the biology of herpes viruses, especially Kaposi sarcoma herpes virus that can cause skin cancer. Herpes viruses establish life-long latency in humans and cause the disease upon activation from a latent state to lytic state. We aim to find new genes that play a role in latency establishment, maintenance of latency, reactivation and lytic infection.
1. 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.
2. 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.
3. 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.
4. 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
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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).
11. 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.
12. 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.
13. 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.