2020 Lautenberg Center Progress Report

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18 Publications (<strong>2020</strong>): 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. Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells' heterogeneity. Nature Communication. <strong>2020</strong> Sep 9;11(1):4516.
HEPATIC INFLAMMATION AND METABOLISM AND THEIR INTRICATE RELATIONSHIP WITH LIVER CANCER Eli Pikarsky Lay language summary The liver coordinates our body's response to metabolic stress and governs metabolic availability to other organs. In addition it coordinates multiple immunological functions, and is the organ that harbors the largest numbers of immune cells in our body. Thus the liver is the first organ exposed to all nutrients, drugs, toxins and chemicals that are introduced into the body by ingestion. It is also the place were excess energy is stored in the form of glucose, and upon stress also accumulated fatty acids. 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 inflammation, 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 have discovered that the tumor suppressor gene p53, which is highly important in liver cancer, has a "moonlighting job" in the liver – it regulates multiple metabolic pathways. We discovered that a specific region of p53 – which mostly works as a tumor suppressor – is active in the liver, and also other organs including muscle and pancreas, in regulating glucose and fat homostasis. This could identify drugs which will prevent fatty liver disease progression. 19
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Page 5 and 6: 5 19. Oster S, Aqeilan R.I. Mapping
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Page 9 and 10: NEW THERAPEUTICS TO COMBAT ACUTE MY
Page 11 and 12: 11 PhD students recently graduated:
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Page 21 and 22: 21 11. Hanin G, Yayon N, Tzur Y, Ha
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Page 29 and 30: NATURAL KILLER CELL FUNCTION IN PRE
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Page 35 and 36: 35 Awards: The Rappaport Award for
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Page 39 and 40: 39 21. Emma Hajaj, Galit Eisenberg,
Page 41 and 42: integrate these data and predict on
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2020 Lautenberg Center Progress Report

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