פרופ' רונית אייזנברג שגיא
מופקד על קתדרה בדיקאנט ומנהל הפקולטה לרפואה
מידע כללי
Biography
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 |
תחומי מחקר
Mast cell function in health and disease
The primary interest of the Sagi-Eisenberg group is deciphering the mechanisms that dictate the consequences of mast cell activation. Indeed, mast cells are key effector cells whose activation results in the secretion of multiple inflammatory mediators, such as histamine and cytokines that cause allergic reactions, including skin allergy, food allergy and anaphylaxis. Mast cells derived mediators also play an important role in the amplification of chronic inflammatory diseases, including asthma, bowel diseases, autoimmune diseases, neurodegenerative diseases and cancer. However, on the other side of the coin, mast cells are part of the immune system, whose released mediators play protective roles in host defense mechanisms. Hence, deciphering the molecular mechanisms that drive mast cells from their protective immune functions, to their pathological function in allergy, inflammation and cancer is the focus of our studies. To that end, we combine up-to-date imaging with functional genomics driven screens to identify cellular proteins that control the release process during mast cells activation under experimental settings that recapitulate health and disease. Such proteins could serve as targets for the development of novel drugs that will eradicate the pathological function of mast cells in allergy, inflammation and cancer, while leaving their physiological functions intact.
We are currently recruiting students to participate in the following projects:
1) Secretory granules size and mast cell cancer; Exploring their genetic connections.
2) Migrating or secreting? The mechanism behind the decision-making.
3) Mast cells and cancer- how to turn bad into good.
4) Autophagy in mast cells –death or survival?
Publications & Grants
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
