Name: Eli Pikarsky

 Title： MD PhD

 Email: peli@hadassah.org.il

 Tel: 972-50-8573237

Research Interests

Our longstanding interest in to understand heterotypic cell interactions, in the context of liver tissue, and their contribution to disease, focusing on interactions between epithelial and immune cells. In recent years we are studying a very common form of liver inflammation – formation of immune cell aggregated termed Ectopic Lymphoid Like structures (ELSs). It was known that ELSs can for frontal command posts that fight tumors, but we discovered that in specific settings, which are very common in certain diseases such as Hepatitis C infection, ELSs can be protumorigenic. We are now deciphering the mechanisms that underlie the transition from anti-tumor to pro-tumor immunity.

Fat accumulation in the liver is caused by excess energy intake, or by deranged ability of the liver to metabolize and export fatty acids. Accumulation of fatty acids in the liver is one of the most common causes of liver inflammation and liver cancer: fatty liver disease. This has become an epidemic, affecting nearly 25% of the population and is now also seen in obese adolescents and even children. Fatty liver disease often progresses to a more severe form denoted steatohepatitis – due to the appearance of an inflammatory component. Yet the mechanisms that induce such progression are not known. We are using different mouse models of fatty liver disease to assess the role of inflammation related signaling pathways and their contribution to disease progression. These may be altered in either the hepatocytes or the liver immune cells. In the long range we aim to utilize the gained knowledge to identify drugs which will prevent fatty liver disease progression.

Ten Selected Papers

*co-corresponding authors; #co-first authors

1. Pikarsky E. Neighbourhood deaths cause a switch in cancer subtype. Nature. 2018; 562:45-6.

2. Finkin S, Yuan D, Stein I, Taniguchi K, Weber A., . . . Karin M, Heikenwalder M*, Ben-Neriah Y* & Pikarsky E*. Ectopic lymphoid structures as microniches for tumor progenitor cells.  Nat Immunol. 2015;16:1235-44.

3. Hefetz-Sela S, Stein I, Klieger Y, Porat R, Sade-Feldman M., . . . Wagner EF, Ben-Neriah Y, Baniyash M & Pikarsky E. Acquisition of an Immunosuppressive Pro-Tumorigenic Macrophage Phenotype Depends on c-Jun Phosphorylation. Proc Natl Acad Sci USA. 2014; 111:17582–87.

4. Horwitz A, Stein I, Andreozzi M, Nemeth J, Shoham A., . . . Angel P, Ben-Neriah Y* & Pikarsky E*. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. Cancer Discovery. 2014; 4:730-43.

5. Pribluda A, Elyada E, Wiener Z, Hamza H, Goldstein RE., . . . Stiewe T, Oren M, Alitalo K, Pikarsky E* & Ben-Neriah Y*. A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell. 2013; 24:242-56.

6. Elyada E, Pribluda A, Goldstein RE, MorgensternY, Brachya G., . . . Alitalo K, Oren M, Pikarsky E* & Ben-Neriah Y*. CKIalpha ablation highlights a critical role of p53 in invasiveness control. Nature. 2011; 470:409-13.

7. Biton M, Levin A, Slyper M, Alkalay I, Horwitz E, . . . Artis D, Hornstein E, Pikarsky E* & Ben-Neriah Y*. Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nature Immunology. 2011; 12:239-46.

8. Gielchinsky Y, Laufer N, Abramovitch R, Granot Z, Bergman Y & Pikarsky E. Pregnancy restores the regenerative capacity of the aged liver via activation of an mTOR-controlled hyperplasia/hypertrophy switch. Genes Dev. 2010; 24:543-48.

9. Pikarsky E#*, Porat RM#, Stein I#, Abramovitch R, Amit S., . . . Galun E & Ben-Neriah Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004; 431:461-6.

10. Gidekel S, Pizov G, Bergman Y & Pikarsky E. Oct-3/4 is a dose-dependent oncogenic Fate determinant. Cancer Cell. 2003; 4:361-70.