Center for Autoimmune Liver Diseases Research Laboratory – Dr Ehud Zigmond >>

Center for Autoimmune Liver Diseases Research Laboratory

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Our Vision

Our group is broadly interested in understanding the role of the innate immune system, and in particular of mononuclear phagocytes, in the development and progression of autoimmune liver diseases and inflammatory gut disorders. We study the function of these cells in their physiological context under steady state and pathological conditions of cholangitis, hepatitis and colitis. Our study combines in vivo techniques as well as immunological and molecular skills.

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Contact Us

Primary Investigators
Udi Zigmond

Dr Ehud Zigmond MD, PhD - Lab PI

Phone: +972-52-7360021
Email: zigmond@tlvmc.gov.il

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Dr Debby Reuveni PhD - Lab Manager

Phone: +972-54-6420343
Email: dhaita@gmail.com

Address

Sourasky building

‎1st floor ‎,Above gate 6 Sourasky Medical Center,‎
Weizmann 6 st’, 64239‎ Tel-Aviv, Israel‎

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Research

Unravelling the role of Tarm1 in the pathogenesis of inflammatory gut and liver disorders

TARM-1 (T Cell-Interacting, Activating Receptor on Myeloid Cells 1) is a recently discovered receptor that belongs to the Leukocyte Receptor Complex (LRC) family. It is expressed predominantly by myeloid cells, specifically by macrophages and neutrophils. The role and function of this receptor in the regulation of the immune system in inflammatory conditions is largely unknown.

Inflammatory Bowel Diseases (IBD) are chronic immune-related disorders of the gastrointestinal tract. Previous studies have shown that neutrophils and mononuclear phagocytes play a crucial role in the pathogenesis of IBD. We have found increased intestinal expression levels of TARM-1 in murine acute and chronic colitis models, as well as in intestinal samples of IBD patients.

We have developed conditional transgenic TARM-1 deficient mice to study its cell specific biology in intestinal inflammation and other inflammatory disorders.

Studying the involvement of monocytes and specific types of Dendritic cells in the pathogenesis of Primary Biliary Cholangitis

Primary Sclerosing Cholangitis (PSC) is chronic cholestatic liver disease characterized by concentric and obliterative fibrosis of the bile ducts. Unfortunately, therapeutic options for PSC are currently limited and have largely failed to change the poor natural history of the disease.

Monocyte-derived cells were shown to be important for the pathologic process of cholangitis and sclerosis in PSC animal models. Yet, the mechanisms involved including the cellular interactions within this unique fibrotic niche are unknown. In collaboration with prof. Shalev Itzkovitz lab at the Weizmann institute of science, we take advantage of next-generation single cell spatial molecular profiling techniques and other state of the art RNA sequencing and imaging methods to uncover the molecular profiling of sclerosing cholangitis in a cellular level and inter-cellular levels. We believe that this research approach will uncover potential targets for novel therapeutic interventions for the benefit of PSC patients.

Identifying the interaction between macrophage and key cellular components within the portal fibrotic niche in Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis (PSC) is chronic cholestatic liver disease characterized by concentric and obliterative fibrosis of the bile ducts. Unfortunately, therapeutic options for PSC are currently limited and have largely failed to change the poor natural history of the disease.

Monocyte-derived cells were shown to be important for the pathologic process of cholangitis and sclerosis in PSC animal models. Yet, the mechanisms involved including the cellular interactions within this unique fibrotic niche are unknown. In collaboration with prof. Shalev Itzkovitz lab at the Weizmann institute of science, we take advantage of next-generation single cell spatial molecular profiling techniques and other state of the art RNA sequencing and imaging methods to uncover the molecular profiling of sclerosing cholangitis in a cellular level and inter-cellular levels. We believe that this research approach will uncover potential targets for novel therapeutic interventions for the benefit of PSC patients.

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Our Team

Current Staff

Lab manager

Students

Basic Science Project

Basic Science Project

Past Staff

Lab manager

Research Associate

Students

Volunteers

Current funding

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Highlight Publications

Real-World Management of Patients with Primary Biliary Cholangitis-A Retrospective Study from a Tertiary Medical Center in Israel.

Yehezkel E, Israel I, Houri I, Leshno M, Shibolet O, Zigmond E.  J Clin Med. 2021 Sep 30;10(19):4551.

Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis.

Reuveni D, Brezis MR, Brazowski E, Vinestock P, Leung PSC, Thakker P, Gershwin ME, Zigmond E. Front Immunol. 2021 Aug 13;12:718841.

Acute liver failure is regulated by MYC- and microbiome-dependent programs.

Kolodziejczyk AA, Federici S, Zmora N, Mohapatra G, Dori-Bachash M, Hornstein S, Leshem A, Reuveni D, Zigmond E, Tobar A, Salame TM, Harmelin A, Shlomai A, Shapiro H, Amit I, Elinav E. Nat Med. 2020 Dec;26(12):1899-1911.

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Two Roads Diverge in the Sick Liver, Monocytes Travel Both.

Zigmond E, Varol C. Immunity. 2020 Sep 15;53(3):479-481.

The challenges of primary biliary cholangitis: What is new and what needs to be done.

Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Björnsson E, Bowlus C, Carbone M, Chazouillères O, Dalekos G, De Gottardi A, Harada K, Hirschfield G, Invernizzi P, Jones D, Krawitt E, Lanzavecchia A, Lian ZX, Ma X, Manns M, Mavilio D, Quigley EM, Sallusto F, Shimoda S, Strazzabosco M, Swain M, Tanaka A, Trauner M, Tsuneyama K, Zigmond E, Gershwin ME. J Autoimmun. 2019 Dec;105:102328.

 

Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer.

Bar-David S, Larush L, Goder N, Aizic A, Zigmond E, Varol C, Klausner J, Magdassi S, Nizri E. Sci Rep. 2019 Jun 12;9(1):8566.

Klotho suppresses colorectal cancer through modulation of the unfolded protein response.

Arbel Rubinstein T, Shahmoon S, Zigmond E, Etan T, Merenbakh-Lamin K, Pasmanik-Chor M, Har-Zahav G, Barshack I, Vainer GW, Skalka N, Rosin-Arbesfeld R, Varol C, Rubinek T, Wolf I. Oncogene. 2019 Feb;38(6):794-807.

High frequency of multiclass HCV resistance-associated mutations in patients failing direct-acting antivirals: real-life data.

Gozlan Y, Bucris E, Shirazi R, Rakovsky A, Ben-Ari Z, Davidov Y, Veizman E, Saadi T, Braun M, Cohen-Naftaly M, Shlomai A, Shibolet O, Zigmond E, Katchman H, Menachem Y, Safadi R, Galun E, Zuckerman E, Nimer A, Hazzan R, Maor Y, Saif AM, Etzion O, Lurie Y, Mendelson E, Mor O. Antivir Ther. 2019;24(3):221-228.

 

The Critical Role of Chemokine (C-C Motif) Receptor 2-Positive Monocytes in Autoimmune Cholangitis.

Reuveni D, Gore Y, Leung PSC, Lichter Y, Moshkovits I, Kaminitz A, Brazowski E, Lefebvre E, Vig P, Varol C, Halpern Z, Shibolet O, Gershwin ME, Zigmond E. Front Immunol. 2018 Aug 15;9:1852.

Erythropoietin enhances Kupffer cell number and activity in the challenged liver.

Gilboa D, Haim-Ohana Y, Deshet-Unger N, Ben-Califa N, Hiram-Bab S, Reuveni D, Zigmond E, Gassmann M, Gabet Y, Varol C, Neumann D. Sci Rep. 2017 Sep 4;7(1):10379.

With Respect to Macrophages, Judge the Liver by Its Cover.

Zigmond E, Varol C. Immunity. 2017 Aug 15;47(2):219-221.

Ly6Chi Monocytes and Their Macrophage Descendants Regulate Neutrophil Function and Clearance in Acetaminophen-Induced Liver Injury.

Graubardt N, Vugman M, Mouhadeb O, Caliari G, Pasmanik-Chor M, Reuveni D, Zigmond E, Brazowski E, David E, Chappell-Maor L, Jung S, Varol C. Front Immunol. 2017 Jun 1;8:626.

Oral Administration of β-Glucosylceramide for the Treatment of Insulin Resistance and Nonalcoholic Steatohepatitis: Results of a Double-Blind, Placebo-Controlled Trial.

Lalazar G, Zigmond E, Weksler-Zangen S, Ya’acov AB, Levy MS, Hemed N, Raz I, Ilan Y. J Med Food. 2017 May;20(5):458-464.

 

Intraoperative Localization of Rectal Tumors Using Liposomal Indocyanine Green.

Magdassi S, Bar-David S, Friedman-Levi Y, Zigmond E, Varol C, Lahat G, Klausner J, Eyal S, Nizri E. Surg Innov. 2017 Apr;24(2):139-144.

HCV genotype-1 subtypes and resistance-associated substitutions in drug-naive and in direct-acting antiviral treatment failure patients.

Gozlan Y, Ben-Ari Z, Moscona R, Shirazi R, Rakovsky A, Kabat A, Veizman E, Berdichevski T, Weiss P, Cohen-Ezra O, Lurie Y, Gafanovich I, Braun M, Cohen-Naftaly M, Shlomai A, Shibolet O, Zigmond E, Zuckerman E, Carmiel-Haggai M, Nimer A, Hazzan R, Maor Y, Kitay-Cohen Y, Shemer-Avni Y, Kra-Oz Z, Schreiber L, Peleg O, Sierra S, Harrigan PR, Mendelson E, Mor O.  Antivir Ther. 2017;22(5):431-441.

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