פרופ' רות שלגי חרסינה

ביולוגיה תאית והתפתחותית אמריטוס
פרופ' רות שלגי חרסינה
טלפון פנימי: 03-6408685
פקס: 03-6407432
משרד: רפואה-סאקלר, 305

Positions

Professor, Department of Cell and Development Biology, Sackler Faculty of Medicine

Gabriel Pinkas Chair for the Prevention and Diagnosis of Congenital Anomalies

Executive Committee, Open University, Member

 

Biography

Education

1971-1977 Ph.D., Tel Aviv University
1969-1971 M.Sc. (Cum Laude), Zoology, Tel Aviv University
1966-1969 B.Sc., Biology, Tel Aviv University

1969 -1974 Tel Aviv University, Israel, Dept. of Zoology, Assistant
1974 -1977 Tel Aviv University, Israel, Dept. of Zoology, Instructor
1977 -1979 Rockefeller University, NY, Population Council, Postdoctoral Fellow
1980 -1984 Tel Aviv University, Israel, Dept. of Embryology and Teratology, Lecturer
1984 -1991 Tel Aviv University, Israel, Dept. of Embryology and Teratology, Senior Lecturer
1987 Babraham Institute, Cambridge UK, Dept.of Molecular, Embryol., Visiting Scientist
1987 Roche Inst of Molecular Biology, NJ, Dept. Cell & Develop. Biol.,Visiting Scientist
1990 University of Hawaii, HA, Dept. Anatomy & Reproductive Biol., Visiting Scientist
1991-1996 Tel Aviv University, Israel, Dept. of Embryology & Teratology, Associate Professor
1996-present Tel Aviv University, Israel, Dept. Cell & Developmental Biology, Professor

1997-2001 Tel Aviv University, Israel, Dean of students
2001- 2005 Tel Aviv University, Israel, Vice President and Dean for Research
2006-present Gabriel Pinkas Chair for the prevention and diagnosis of congenital anomalies.
2006- 2010 Tel Aviv University, Israel, Vice Dean for Preclinical Affairs, Faculty of Medicine

תחומי מחקר

 

Reproduction in animal models and in humans

 

Our research focuses on Reproductive Physiology in animal models and in humans. The current research directions investigated in the laboratory are:

• The role of Pigment epithelium derived factor (PEDF) in ovarian physiology and infertility.


• The role of Fyn kinase, member of the Src family kinases, during meiosis and early events of oocyte activation, as well as in cancer cells (Figure-left panel).

• Fertility preservation - the signaling pathway leading to apoptosis in aging oocytes and in oocytes exposed to chemotherapeutic treatments and potential protectants (Figure -right panel).

Various research methods are routinely used in the laboratory, ranging from in vivo animal studies and cells cultures to an array of protein methodologies such as western blotting, immunohistochemistry, molecular biology techniques as well as cellular and molecular imaging.

 

פרסומים

Publications (last 5 years)

Levi M and Shalgi R. The role of fyn kinase in the release from metaphase in mammalian oocytes. Mol. Cell. Endocr. 314: 228-233, 2010.

 

Ben-Aharon, I., Bar-Joseph, H., Tzarfaty, G., Kuchinsky, L., Rizel, M., Stemmer, S.M. and Shalgi, R. Doxorubicin-induced ovarian toxicity. Reprod. Biol. Endocr. 8: 20-26, 2010. PMID: 20202194

 

Levi M, Maro B and Shalgi R. The involvement of Fyn kinase in resumption of the first meiotic division in mouse oocytes. Cell cycle. 9 (8): 1577-1589, 2010. PMID: 20372074

 

Bar-Joseph, H., Ben-Aharon, I., Rizel, S., Stemmer, S.M., Tzabari, M. and Shalgi, R. Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes. Reprod. Toxicol. Dec; 30(4):566-72, 2010. PMID: 20656019.

 

Levi, M., Maro, B. and Shalgi R. Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis. Reproduction. 140: 827-834, 2010. PMID:20841362

 

Haberman, Y., Tsaadon, L., Eliyahu, E., and Shalgi, R. Receptor for activated C kinase (RACK) facilitates protein kinase C (PKC) mediated cortical granules exocytosis (CGE). Theriogenology, Jan 75 (1): 80-9, 2011. PMID: 20843544

 

Levi, M., Kraicer-Kaplan, R. and Shalgi, R. Regulation of division in mammalian oocytes: Implications for polar body formation. Review. Mol. Hum. Reprod. May 17 (5) 324-338, 2011. PMID:21498869. PMID:21498869

 

Levi, M., Maro, B. and Shalgi R. The conformation and activation of Fyn kinase in the oocyte determine its localization to the spindle poles and cleavage furrow. Reprod. Fertil. Dev. 23: 846-857, 2011. PMID: 21871204

 

Bar-Joseph, H., Ben-Aharon, I., Stemmer, S.M., Tzabari, M. and Shalgi, R. Novel in vivo imaging of acute chemotherapy-induced vascular toxicity. PLos One: 9 (6) e23492 Sep 2011. PMID: 21931602

 

Ben-Aharon, I. and Shalgi, R. What lies beyond chemotherapy induced ovarian toxicity (Review). Reproduction, June 144: 153-163, 2012. PMID 22653316.

 

Eliyahu E, Shtraizent N, He X, Chen D, Shalgi R. and Schuchman E. Identification of cystatin SA as a novel inhibitor of acid ceramidase. J. Biol. Chem. 286: 35624-33, Oct. 2011. PMID: 21846728

 

Levi, M., Ninio-Mani, L. and Shalgi R. SRC protein kinases in mouse and rat oocytes and embryos. Chapter 4 submitted to the book: "Mouse Development: From Oocyte to Stem Cells"; Results Probl Cell Differ. 55:93-106, 2012. PMID: 22918802.

 

Chuderland*, D., Ben-Ami* I., Ronel, R., Kraicer-Kaplan, R., Grossman, H., Satchi- Fainaro, R., Eldar-Boock, A. and, Shalgi, R. Hormonal regulation of pigment epithelium derived factor (PEDF) in granulosa cells. Mol Hum Reprod. Nov 2012 PMID: 23075882

 

Chuderland*, D., Ben-Ami* R., Kraicer-Kaplan, R., Grossman, H., I., Ronel, and, Shalgi, R. Pigment epithelium-derived factor as a replacement therapy for ovarian hyper-stimulation syndrome in mice. J Clin. Endocr. Metab. Feb;19(2):72-81 2013. PMID: 23295464

 

Chuderland, D.*, Hasky, N.*, Ben-Ami, I., Kaplan-Kraicer, R., Grossman, H. and Shalgi R. A physiological approach for treating endometriosis by recombinant pigment epithelial derived factor (PEDF). Hum. Reprod. 28(6): 1626-34, 2013 [Epub 2013 Mar 6]. PMID: 23466670

 

Ninio-Many, L., Grossman, H., Shomron, N., Chuderland D. and Shalgi, R. microRNA-125a-3p reduces cell proliferation and migration by targeting Fyn. J. Cell Sci, Jul 1; 126 (3): 2867-2876,  2013. PMID 23606749.

 

Levi M, Ghetler Y, Shulman A and Shalgi, R. Morphologic and molecular markers indicate maturation-competence of human oocytes. Hum. Reprod. 28(9) 2482–2489, 2013.   (4.67 2/28 Reprod. Biol.)  PMID 23787211

 

Ben Aharon, I., Bar Joseph, H., Tzabari, M., Shekman, B., Farzam, N., Levi, M., Shalgi, R., Stemmer, SM. and Savion, N. Doxorubicin-induced vascular toxicity – Targeting potential pathways may reduce procoagulant activity. PLos One, 8 (9) e75157 Sep 20, 2013 PMID: 24073244

 

Chuderland D., Ben-Ami, I., Fridler, S., Hasky, N., Ninio-Many, L., Goldberg, K., Bar-Josef, H., Grossman, H., and Shalgi, R. ¬¬Hormonal regulation of Pigment epithelium-derived factor  (PEDF) expression in the endometrium. Mol. Cell Endocrinol. 390, 85-92, 2014.
Epub 2014 Apr 24. 2014 Jun 5; 390(1-2):85-92. PMID: 24769282
 

Ninio-Many, L., Grossman, H., Levi, M., Zilber, S., Tsarfaty, I., Shomron, N., Tuvar, A., Chuderland D., Stemmer, S.M., Ben-Aharon, I.* and Shalgi R.* MicroRNA miR-125a-3p modulates molecular pathway of motility and migration in prostate cancer cells. Oncoscience. April 30;1(4), 250-261, 2014. eCollection 2014  PMID: 25594017
  
Bar-Joseph, H., Ido Ben-Ami, I., Ron-El, R., Shalgi, R*. and Chuderland, D*. Pigment epithelium-derived factor (PEDF) exerts anti oxidative effects in granulosa cells.  Feril. Steril. Sep;102(3):891-898.e3. 2014
doi: 10.1016/j.fertnstert.2014.06.012. [Epub 2014 Jul 23]  PMID: 25064413

 

Chuderland, D., Ben-Ami, I., Bar-Joseph, H. and Shalgi, R. Pigment epithelium-derived factor (PEDF) in the reproductive system. Reproduction. 2014 Oct;148(4):R53-R61. Review. PMID: 25049425

 

Uri-Belapolsky, S., Shaish, A., Eliyahu, E., Grossman, H., Levi, M., Chuderland, D., Ninio-Many, L., Hasky, N., Shashar, D., Almog, T., Kandel-Kfir, M., Harats, D., Shalgi, R.* and Kamari, Y*. Interleukin-1 deficiency prolongs ovarian lifespan in mice. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12492-7 2014.  PMID: 25114230]


*Recommended by F1000Prime Interleukin-1 deficiency prolongs ovarian lifespan in mice. Rep. 2014; 6: Published online Sep 10, 2014.

 

Yesilaltay, A., Dokshin, G., Busso, D., Galiani, D., Chavarria, T.E., Vasile, E., Quilaqueo, L., Shalgi, R., Dekel, N., Albertini, D., Rigotti, A., Page, D.C., Krieger, D.C. Excess cholesterol induces mouse oocyte activation and may cause infertility. Proc Natl Acad Sci U S A. Nov 18;111(46):E4972-80. 2014.PMID: 25368174 

 

  * Highlighted by Charlotte Schubert in "World of Reproductive Biology":Cholesterol Overload Damages Eggs. Biol Reprod February 2015 92 (2) 30, 1-1

Bar-Joseph, H., Stemmer, S.M., Tsarfaty, I., Shalgi, R. and  Ben Aharon, I. Chemotherapy -induced vascular toxicity – Real-time in vivo imaging of vessel impairment. J. Vis. Exp. Jan 7:(95), e51650, doi:10.3791/51650; 2015. PMID: 25590564 [PubMed]

 

Hasky, N., Uri-Belapolsky S., Goldberg, K., Miller, I., Grossman, H., Stemmer, S.M. Ben-Aharon, I*. and Shalgi, R*. Gonadotropin-releasing hormone agonists for fertility preservation – unraveling the enigma? Hum. Reprod. 30 (5): 1089–1101, 2015
Advanced Access publication Mar 21  PMID: 25796551

 

Ninio-Many, L., Shalgi, R. and Ben-Aharon, I. miR-125a - Does the difference lie in the isoform? Cell Cycle Mar 19;14(6):785-6. 2015. PMID: 25790088

 

Grossman, H., Chuderland, D., Ninio-Many, L., Hasky, N., Kaplan-Kraicer, R. and Shalgi, R. A novel regulatory pathway in granulosa cells, the LH/human chorionic gonadotropin-microRNA-125a-3p-Fyn pathway, is required for ovulation. FASEB J Aug;29 (8):3206-16, 2015 Epub 2015 Apr 28, 

  

Levi, M., Tzabari M., Savion, N., Stemmer, S.M., Shalgi, R.* and Ben-Aharon, I.* Dexrazoxane exacerbates doxorubicin-induced testicular toxicity. Reproduction. 150(4) 357–366, 2015. PMID: 26329125

 

Levi, M., Hasky, N., Stemmer, S.M., Shalgi, R.* and Ben-Aharon, I.*. Anti Müllerian hormone is a marker for chemotherapy-induced testicular toxicity. Endocrinology. Oct;156(10):3818-27. 2015. PMID: 26252060 

 

Miller, I., Chuderland, D., Ron-El R., Shalgi, R.* and Ben-Ami, I.* – GnRH agonist triggering modulates PEDF/VEGF ratio inversely to hCG in granulosa cells.  J Clin Endocrinol Metab. Nov 100(11):E1428-36. doi: 10.1210/jc.2015-2312. Epub Aug 26. PMID: 26308290

 

*Highlighted by Robert Casper in "Reducing the risk of OHSS by GnRH agonist triggering".  J Clin Endocr Metab. 2015; Oct 29:jc20153676. [Epub] PMID: 26513003

 

Levi, M., Shalgi, R., Brenner, B., Perl, G., Purim, O., Amit, L., Stemmer, S.M. and Ben-Aharon, I. The impact of oxaliplatin on the gonads – from bedside to the bench. Mol Hum Reprod Dec;21(12):885-93 2015. Epub 2015 Oct 6.  PMID: 26443807

 

Goldberg, K., Bar Joseph, H., Grossman, H., Hasky, N., Uri-Belapolsky, S., Stemmer, S.M., Chuderland, D*., Shalgi, R.* and Ben-Aharon, I.* Pigment epithelium-derived factor alleviates tamoxifen-induced endometrial hyperplasia. Mol Cancer Ther. Dec;14(12):2840-9  2015. Epub 2015 Oct 8.  PMID: 26450919

 

Bar-Joseph, H., Ben-Ami, I., Ron-El, R., Shalgi, R.* and Chuderland, D*. Pigment epithelium-derived factor (PEDF) regulation by hCG in granulosa cells. Reproduction 151 (2) 179-185,  2016. Epub Nov 26. 2015 PMID: 26612427

 

Levi, M., Popovtzer, A., Tzabari, M., Mizrachi, A., Savion, N., Stemmer, S.M., Shalgi, R. and Ben-Aharon, I. Cetuximab intensifies cisplatin-induced testicular toxicity. Reprod Biomed Online. 2016 Jul;33(1):102-10; 2016 Epub ahead of print April 2016 PMID: 27184186

 

Grossman, H. and Shalgi, R. A Role of microRNAs in cell differentiation during gonad development. Review In: Springer International Publishing Switzerland; R.P. Piprek (ed.), Molecular Mechanisms of Cell Differentiation in Gonad Development: Results and Problems in Cell Differentiation 58, Chapter 12, pp 309-336, 2016. PMID: 27300184

 

Miller, I., Chuderland, D., Grossman, H., Ron-El R., Ben-Ami, I.* and Shalgi, R*. The dual role of pigment PEDF in the pathogenesis of OHSS: negating both angiogenic and inflammatory pathways. J Clin Endocrinol Metab. Dec;101(12):4699-4709, 2016. 28 September 2016. PMID: 27680872;  

Uri-Belapolsky, S., Ninio-Many, L., Shaish, A., Levi, M., Harats, D., Kamari, Y*. and Shalgi, R*. Interleukin-1 alpha deficiency increases the expression of follicle-stimulating hormone receptors in granulosa cells. Mol. Reprod. Dev. 2017  DOI: 10.1002/mrd.22799

 

Grossman, H., Har-Paz, E., Gindi N., Irit, M., Levi, M., Nevo, N., Galiani, D., Dekel, N. and Shalgi R. Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments. Sci Rep. 2017 May 22;7(1):2238. PMID: 28533542 

 

Ben-Aharon I, Levi M, Margel D, Yerushalmi R, Rizel S, Perry S, Sharon E, Hasky N, Abir R, Fisch B, Tobar A, Shalgi R, Stemmer SM. remature ovarian aging in BRCA carriers: a prototype of systemic precocious aging? Oncotarget. 2018 Mar 23; 9 (22):15931-15941.

 

doi: 10.18632/oncotarget.24638. eCollection 2018 Mar

 

161. Levi, M., Stemmer, S.M., Stein, J., Shalgi, R. and Ben-Aharon, I. Treosulfan induces differential gonadal toxicity profile compared with Busulfan. Oncotarget 2018 Apr 10;9(27):19317-19327.

 

doi: 10.18632/oncotarget.25029. eCollection 2018 Apr 10. PMID: 29721205

 

Mizrachi, A., Ben-Aharon, I., Li, H., Bar-Joseph, H., Bodden, C., Hikri, E., Popovtzer, A., Shalgi, R. and Haimovitz-Friedman, A. Activation of the acid sphingomyelinase pathway as mechanism of chemotherapy-induced vascular injury in normal tissues. Sci Rep.

Accepted for Publication

 

אוניברסיטת תל-אביב, ת.ד. 39040, תל-אביב 6997801
UI/UX Basch_Interactive