Prof. Ronit Sagi-Eisenberg

Professor, Cell & Development Biology, Sackler Faculty of Medicine, Tel Aviv University

Chair, Department of Cell and Developmental Biology

Education

1974	B.Sc. in Chemistry, with distinction	Tel Aviv University
1980	Ph.D. in Biochemistry	Tel Aviv University
1980-1984	Postdoctoral fellow	The Weizmann Institute of Science

 

Molecular Basis of Allergic Diseases: Genomic and Functional Analyses

Our primary interest is the molecular basis of allergic and allergy related diseases, including skin allergy and asthma. Specifically, we explore the mechanisms underlying release of allergic (i.e. histamine) and inflammatory (i.e. cytokines) mediators from activated mast cells. Our research focuses on deciphering the signaling networks that link mast cell activation with mediator release and characterization of genes that could serve as cellular targets for the future development of anti allergic and asthma drugs. To this end, we combine functional genomics and phenotype driven screens of mast cells, activated by multiple stimuli, in order to recapitulate human pathophysiologic conditions. Research methods used include confocal microscopy in live and fixed cells; gene cloning; quantitative RT-PCR, pull down-assay; mass spectrometry, and bioinformatics.

 

Current projects in the lab include:                                          

• Exploring the genetic connections between the size of the mast cell secretory granules and mastocytosis.
• Mast cells and cancer- the good, the bad and the ugly.
• Decoding the Rab networks that control mast cell function.

 

Recent Publications

 

Klein O, Krier-Burris RA, Lazki-Hagenbach P, Gorzalczany Y, Mei Y, Ji P, Bochner BS, Sagi-Eisenberg R. mDia1 coordinates mast cell migration and secretion through its actin nucleating activity.

J Allergy Clin Immunol. 2019 Jul 3. pii: S0091-6749(19)30890-5. doi: 10.1016/j.jaci.2019.06.028. [Epub ahead of print]

 

Select item 29985342Klein O, Roded A, Hirschberg K, Fukuda M, Galli SJ, Sagi-Eisenberg R.

 Imaging FITC-dextran as a Reporter for Regulated Exocytosis. J Vis Exp. 2018 Jun 20;(136). doi: 10.3791/57936.

 

Klein O, Roded A, Zur N, Azouz NP, Pasternak O, Hirschberg K, Hammel I, Roche PA, Yatsu A, Fukuda M, Galli SJ, Sagi-Eisenberg R. Rab5 is critical for SNAP23 regulated granule-granule fusion during compound exocytosis. Sci Rep. 2017 Nov 10;7(1):15315. doi: 10.1038/s41598-017-15047-8.

 

Gorzalczany Y, Akiva E, Klein O, Merimsky O, Sagi-Eisenberg R. Mast cells are directly activated by contact with cancer cells by a mechanism involving autocrine formation of adenosine and autocrine/paracrine signaling of the adenosine A3 receptor. Cancer Lett. 2017 Jul 1;397:23-32. doi: 10.1016/j.canlet.2017.03.026. Epub 2017 Mar 22.

 

Gaudenzio N, Sibilano R, Marichal T, Starkl P, Reber LL, Cenac N, McNeil BD, Dong X, Hernandez JD, Sagi-Eisenberg R, Hammel I, Roers A, Valitutti S, Tsai M, Espinosa E, Galli SJ. Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest. 2016 Oct 3;126(10):3981-3998. 

 

Efergan A, Azouz NP, Klein O, Noguchi K, Rothenberg ME, Fukuda M, Sagi-Eisenberg R. Rab12 regulates retrograde transport of mast cell secretory granules by interacting with the rilp-dynein complex. J Immunol. 2016;196:1091-101.

 

Azouz NP, Fukuda M, Rothenberg ME, Sagi- Eisenberg R. Investigating mast cell secretory granules; from biosynthesis to exocytosis. J Vis Exp. 2015;95:52505.

 

Rudich N, Dekel O, Sagi-Eisenberg R. Downregulation of the A3 adenosine receptor in human mast cells upregulates mediators of angiogenesis and remodeling. Mol Immunol. 2015;65:25-33.

 

Azouz, N.P., Zur, N., Efergan, Ohbayashi, N., Fukuda, M., Amihai, D., Hammel, I., Rothenberg^, ME and Sagi-Eisenberg, R. Rab5 is a novel regulator of mast cell secretory granules: impact on size, cargo and exocytosis. J Immunol. 192:4043-53 (2014)

 

Bar-Gill-Benado, A., Efergan, A., Seger, R., Fukuda, M., and Sagi-Eisenberg R. The extra-cellular signal regulated kinases ERK1 and ERK2 segregate displaying distinct spatiotemporal characteristics in activated mast cells. Biochim Biophys Acta. 1833, 2070-2082, (2013).

 

Bernstein-Molho R., Kollender, Y., Issakov, J., Bickels, J., Dadia S., Flusser, G., Meller, I., Sagi-Eisenberg. R. and Merimsky O. Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas. Cancer Chemother Pharmacol. 70, 855-860, (2012).

 

Azouz NP, Matsui, T., Fukuda, M. and Sagi-Eisenberg, R. Decoding the regulation of mast cell exocytosis by networks of Rab GTPases. J Immunol. 189, 2169-2180. (2012).

 

Gorzalczany Y, Gilad Y, Amihai D, Hammel I, Sagi-Eisenberg R, and Merimsky O. Combining an EGFR directed tyrosine kinase inhibitor with autophagy-inducing drugs: a beneficial strategy to combat non-small cell lung cancer. Cancer Lett. 310:207-215. (2011).

 

Baram D, Dekel O, Mekori YA, and Sagi-Eisenberg R. Activation of mast cells by trimeric G protein Gi3; coupling to the A3 adenosine receptor directly and upon T cell contact. J Immunol. 184:3677-3688. (2010).

 

Review

 

Gorzalczany Y, Sagi-Eisenberg R. Role of Mast Cell-Derived Adenosine in Cancer. Int J Mol Sci. 2019 May 27;20(10). pii: E2603. doi: 10.3390/ijms20102603

 

Klein O, Sagi-Eisenberg R. Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis. J Immunol Res. 2019 Mar 18;2019:9542656. doi: 10.1155/2019/9542656.

 

Falcone FH, Wan D, Barwary N, Sagi-Eisenberg R. RBL cells as models for in vitro studies of mast cells and basophils. Immunol Rev. 2018 Mar;282(1):47-57.

 

Rudich N, Ravid K, and Sagi-Eisenberg R. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation. Front Immunol. 3:134. (2012).

 

Siebenhaar F, Falcone FH, Tiligada E, Hammel I, Maurer M, Sagi-Eisenberg R, Levi-Schaffer F. The search for Mast Cell and Basophil models – Are we getting closer to pathophysiological relevance? Allergy 2015;70:1-5.

 

Grants

 

2014-2018  Binational Science Foundation Mast cell exocytosis as a paradigm for the evolution of organismal host defense mechanisms

 

2015-2019 The Israel Science Foundation The role of the small GTPase Rab12 in mast cell degranulation and trafficking of the secretory granules

 

2017-2018 Israel Ministry of Health An in-vitro screening assay for the detection of pseudoallergenic drugs.

 

2018-2022 Binational Science Foundation  Elucidating the roles of the small GTPase Rab5 in regulating mast cell secretory granule biogenesis and compound exocytosis

 

2018-2021 The Israel Ministry of Science and Technology Targeting adenosine activity in the brain in Alzheimer’s disease as a therapeutic application

 

2019-2024 The Israel Science Foundation Mechanisms, regulation and significance of secretory granule positioning in mast cells  

 

2012-2015 The Israel Science Foundation, Dissecting the molecular mechanisms underlying mast cell exocytosis; new insights provided by the small GTPase Rab5

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