Meir Shamay Lab
Daniella Lee Casper Laboratory in Viral Oncology
Welcome to Meir Shamay Lab (MeirShamayLab.com), the viral oncology lab at the Azrieli Faculty of Medicine, Bar-Ilan University. About 15% of cancer cases are associated with viral infections. The two herpes viruses we study, Kaposi’s sarcoma-associated herpesvirus (KSHV, HHV-8) and Epstein-Barr virus (EBV, HHV-4), are associated with an increasing number of human malignancies. The research interests in the lab are to study the functional interactions between viral proteins and the cellular machinery, which control both the viral life cycle and tumorigenesis. The goal of our lab is to expand our knowledge of viral infections and to utilize this knowledge for the development and use of drugs that specifically target virally infected cells.
Research Interests
Our scientific question is how viruses promote cancer development
The research interests in the lab are to study the functional interactions between viral proteins and the cellular machinery, which control both the viral life cycle and tumorigenesis. About 15% of the cancers in humans are associated with viral infections. The viruses we study are the human gamma herpes viruses, Kaposi’s sarcoma-associated herpesvirus (KSHV, HHV-8), and Epstein-Barr virus (EBV, HHV-4), which are associated with an increasing number of human malignancies. EBV is a ubiquitous virus that infects over 90% of adults worldwide, including Israel. KSHV prevalence varies significantly depending on the geographic regions; in Israel, about 10% are infected. While in most infected individuals, these viruses do not lead to cancer development, under specific conditions such as suppression of the immune system, they promote cancer development. The goal of our lab is to expand our knowledge of viral infections and to utilize this knowledge for the development and use of drugs that specifically target virally infected cells.
We have a specific interest in understanding how these viruses modulate our epigenome. Epigenetic marks such as DNA methylation, histone modifications, and chromatin remodeling are important regulators of gene expression. Together with genetic alterations, epigenetic modifications are responsible for the development of many diseases, including cancer. We perform gene-specific and whole-genome DNA methylation analysis and combine these with whole transcriptome (RNA-seq) analysis to reveal the impact of viral infection on DNA methylation and gene expression.
Human endogenous viral elements (EVE) or transposable elements (TEs), as their name suggests, have the ability to transpose (jump) within their host genome. They are ubiquitous in eukaryotic genomes, occupying about 45% of the human genome. Our recent study revealed that KSHV infection dysregulates many transposable elements within the infected cells.
Examples of scientific questions we ask:
1. What are the global epigenetic changes these viruses impose on infected cells during tumor development?
2. Which epigenetic marks differentiate infected cells from infected cells that become cancerous? The results of these studies will help us to develop novel methods for the detection of viral-associated malignancies.
3. How does an exogenous virus like KSHV modulate the expression of human endogenous viruses (transposable elements)?
4. After reading the above, if you have a scientific question related to our study, let’s talk about your next project.
Selected Publications
Cohen-Gulkar M, David A, Messika-Gold N, Eshel M, Ovadia S, Zuk-Bar N, Idelson M, Cohen-Tayar Y, Reubinoff B, Ziv T, Shamay M, Elkon R, Ashery-Padan R. The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration. PLoS Biol. 2023 Jan 17;21(1):e3001924.
Gam Ze Letova C, Kalt I, Shamay M, Sarid R. Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV. Int J Mol Sci. 2021 Nov 5;22(21):11994.
Journo G, Ahuja A, Dias-Polak D, Eran Y, Bergman R and Shamay M. Global CpG DNA Methylation Footprint in Kaposi’s Sarcoma. Front. Cell. Infect. Microbiol., 09 July 2021 | https://doi.org/10.3389/fcimb.2021.666143
Ahuja A, Journo G, Eitan R, Rubin E, Shamay M: High levels of LINE-1 transposable elements expressed in Kaposi's sarcoma-associated herpesvirus-related primary effusion lymphoma. Oncogene. 2020 Nov 13. doi: 10.1038/s41388-020-01549-9.
Naipauer J, Salyakina D, Journo G, Rosario S, Williams S, Abba M, Shamay M, Mesri EA: High-throughput sequencing analysis of a "hit and run" cell and animal model of KSHV tumorigenesis PLoS Pathog. 2020 Jun 30;16(6):e1008589. doi: 10.1371/journal.ppat.1008589. (Shamay M is co-corresponding author).
Shamay M, Kanakry JA, Low JSW, Horowitz NA, Journo G, Ahuja A, Eran Y, Barzilai E, Dann EJ, Stone J, Woo WL, Hsieh WS, Xian RR, Ambinder RF: CpG methylation in cell-free Epstein-Barr virus DNA in patients with EBV-Hodgkin lymphoma. Blood Adv. 2020 Apr 28;4(8):1624-1627. doi:10.1182/bloodadvances.2020001511.
Cohen EM, Avital N, Shamay M, Kobiler O: Abortive herpes simplex virus infection of nonneuronal cells results in quiescent viral genomes that can reactivate. Proc Natl Acad Sci U S A. 2019 Dec 23. pii: 201910537. doi: 10.1073/pnas.1910537117.
Tadmor H, Greenway M, Ahuja A, Orgil O, Liao G, Ambinder RF, Hayward SD, Shamay M: Kaposi's Sarcoma Associated Herpesvirus LANA Modulates the Stability of the E3 Ubiquitin Ligase RLIM. J Virol. 2019 Dec 4. pii: JVI.01578-19. doi: 10.1128/JVI.01578-19.
Journo G, Tushinsky C, Shterngas A, Avital N, Eran Y, Karpuj MV, Frenkel-Morgenstern M, Shamay M: Modulation of Cellular CpG DNA Methylation by Kaposi's Sarcoma-Associated Herpesvirus. J Virol. 2018 Jul 31;92(16).
Simpson S, Fiches G, Jean MJ, Dieringer M, McGuinness J, John SP, Shamay M, Desai P, Zhu J, Santoso NG: Inhibition of Tip60 Reduces Lytic and Latent Gene Expression of Kaposi's Sarcoma-Associated Herpes Virus (KSHV) and Proliferation of KSHV-Infected Tumor Cells. Front Microbiol. 2018 Apr 24;9:788.