Prof. Tsaffrir Zor

Education

• 1989-1991: B.Sc., Chemistry, Hebrew University of Jerusalem , Israel.
• 1992-1997: Ph.D., Biochemistry (Signal Transduction by G-proteins), Hebrew University of Jerusalem, Israel.
• 1998-2003: Post-doctoral research, Structural Biology (transcription regulation), The Scripps Research  Institute, La-Jolla, California, USA.

Current research grants

• Israel Science Foundation (ISF), Identification of receptors for ceramide 1-phosphate (C1P) and modulation of inflammation, 10/2020 – 9/2025, $408,000

Regulation of TNFα and IL-10 expression in macrophages: The pro-inflammatory cytokine TNFα plays a pivotal role in orchestrating innate immune responses that enable us to overcome infections. On the other hand, unregulated production of TNFα may lead to chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. The anti-inflammatory cytokine IL-10 has a key role in limiting the inflammatory response. In our laboratory we study the regulation of TNFα and IL-10 expression and release.

Inflammatory and anti-inflammatory roles of sphingolipids in macrophages – We found that the sphingolipid sulfatide structurally mimics the bacterial pathogen-associated molecular pattern (PAMP) lipopolysaccharide (LPS) and directly bind to its receptor TLR4/MD-2. Short fatty acid chain sulfatides act as agonists and antagonists of mouse and human TLR4/MD-2, respectively. Subsequently, these sulfatides differentially affect inflammation in a species-dependent manner. Our laboratory seeks to identify additional sulfatide receptors involved in inflammation.

For a full list of publications

Selected recent publications

Lijing Su*, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva M.Y. Moresco, Haoming He, Tsaffrir Zor* and Bruce Beutler*, Sulfatides are endogenous ligands for the TLR4/MD-2 complex, Proceedings of the National Academy of Sciences USA, 2021, 118, e2105316118. (pubmed) * co-corresponding author

Orna Ernst, Hila Failayev, Muhammad Athamna, Haoming He, Yossi Tsfadia and Tsaffrir Zor, A dual and conflicting role for imiquimod in inflammation: a TLR7 agonist and a cAMP phosphodiesterase inhibitor, Biochemical Pharmacology, 2020, 182, 114206. (pdf)

Orna Ernst, Yifat Glucksam-Galnoy, Bibek Bhatta, Muhammad Athamna, Iris Ben-Dror, Yair Glick, Doron Gerber and Tsaffrir Zor, Exclusive temporal stimulation of IL-10 expression in LPS-stimulated mouse macrophages by cAMP inducers and type I interferons, Frontiers in Immunology, 2019, 10, 1788, doi: 10.3389/fimmu.2019.01788 (pdf)

Orna Ernst, Yifat Glucksam-Galnoy, Muhammad Athamna, Iris Ben-Dror, Hadar Ben-Arosh, Galit Levy-Rimler, Iain D.C. Fraser and Tsaffrir Zor, The cAMP pathway amplifies early MyD88-dependent and type I interferon-independent LPS-induced interleukin-10 expression in mouse macrophages, Mediators of Inflammation, 2019, Article ID 3451461, 12 pages, doi: 10.1155/2019/3451461 (pdf)

Joram Wardi, Orna Ernst, Anna Lilja, Hussein Aeed, Sebastián Katz, Idan Ben-Nachum, Iris Ben-Dror, Dolev Katz, Olga Bernadsky, Rajendar Kandhikonda, Yona Avni, Iain D.C. Fraser, Roy Weinstain, Alexander Biro and Tsaffrir Zor, 3-aminobenzamide prevents Concanavalin A-induced acute hepatitis in mice by a joint anti-inflammatory and anti-oxidative mechanism, Digestive Diseases and Sciences, 2018, 63, 3382-3397. (pdf)

Sebastián Katz, Orna Ernst, Dorit Avni, Muhammad Athamna, Amir Philosoph, Lide Arana, Alberto Ouro, L. Alexis Hoeferlin, Michael M. Meijler, Charles E. Chalfant, Antonio Gómez-Muñoz and Tsaffrir Zor, Exogenous ceramide-1-phosphate (C1P) and phospho-ceramide analogue-1 (PCERA-1) regulate key macrophage activities via distinct receptors, Immunology Letters, 2016, 169, 73-81. (pdf)

Yifat Glucksam-Galnoy, Roy Sananes, Nava Silberstein, Pnina Krief, Vladimir V. Kravchenko, Michael M. Meijler and Tsaffrir Zor, The bacterial quorum-sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages, Journal of Immunology, 2013, 191, 337-344. (pdf)

Dorit Avni, Yifat Glucksam and Tsaffrir Zor , The Phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 modulates cytokine expression in mouse macrophages via p50 nuclear factor kappa B inhibition, in a PI3K-independent mechanism, Biochemical Pharmacology, 2012, 83, 106-114. (pdf)

Meir Goldsmith, Ala Daka, Nadia F. Lamour, Roi Mashiach, Yifat Glucksam, Charles E. Chalfant, Michael M. Meijler and Tsaffrir Zor, A ceramide analog inhibits cPLA2 activity and consequent PGE2 formation in LPS-stimulated macrophages, Immunology Letters, 2011, 135, 136-143. ( pdf )

Dorit Avni , Orna Ernst , Amir Philosoph and Tsaffrir Zor , Role of CREB in modulation of TNF a and IL-10 expression in LPS-stimulated RAW264.7 macrophages, Molecular Immunology , 2010, 47, 1396-1403. ( pdf )

Orna Ernst and Tsaffrir Zor, Linearization of the Bradford protein assay, Journal of Visualized Experiments, 2010, 38, doi: 10.3791/1918. (video article link) (pdf)

Dorit Avni, Amir Philosoph, Michael M. Meijler and Tsaffrir Zor, The ceramide-1-phosphate analog PCERA-1 modulates TNFα and IL-10 production in macrophages via the cAMP-PKA-CREB pathway in a GTP-dependent manner, Immunology, 2010, 129, 375-385. (pdf)

Maya Levi, Michael M. Meijler, Antonio Gómez-Muñoz, and Tsaffrir Zor , Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1), Molecular and Cellular Endocrinology, 2010, 314, 248-255. (pdf)

Meir Goldsmith, Dorit Avni , Orna Ernst , Yifat Glucksam, Galit Levy-Rimler, Michael M. Meijler and Tsaffrir Zor , Synergistic IL-10 induction by LPS and the ceramide-1-phosphate analog PCERA-1 is mediated by the cAMP and p38 MAP kinase pathways,Molecular Immunology 2009, 46, 1979-1987. (pdf)

Dorit Avni , Meir Goldsmith, Orna Ernst , Roi Mashiach, Tove Tuntland , Michael M. Meijler, Nathanael Gray, Hugh Rosen and Tsaffrir Zor , Modulation of TNFα , IL-10 and IL-12p40 levels by a ceramide-1-phosphate analog, PCERA-1, in-vivo and ex-vivo in primary macrophages, Immunology Letters, 2009, 123, 1-8. (pdf)

Meir Goldsmith, Dorit Avni , Galit Levy-Rimler, Roi Mashiach, Orna Ernst , Maya Levi , Bill Webb, Michael M. Meijler, Nathanael S. Gray, Hugh Rosen and Tsaffrir Zor , A ceramide-1-phosphate analogue, PCERA-1, simultaneously suppresses tumour necrosis factor-α and induces interleukin-10 production in activated macrophages, Immunology, 2009, 127, 103-115. (pdf)