Senior lecturer
M.Sc committee - chairman
- 1997 - 2002 Ph.D. The Kreitman School of Advanced Graduate Studies the Department of Life Sciences, Ben-Gurion Uni. Beer-Sheva, Israel.
- 1993 - 1996 M.Sc. Biology Cum Laude Department of Life Sciences, Ben-Gurion Uni. Beer-Sheva, Israel
- 1988 - 1992 B.Sc. Biology Department of Life Sciences, Ben-Gurion Uni. Beer-Sheva, Israel
- To understand the role of glycosylation on protein functions:
- This include:
- The role of O-GlcNAc post translational modification during cancer development and metastasis.
- The effect of O-GlcNAcylation on hnRNP A1 function with respect to cancer development and metastasis.
- The role of N-glycosylation on lipoprotein interactions and receptor mediated endocytosis.
What is O-GlcNAc protein modification and glycosylation?
- O-GlcNAcylation is a dynamic modification of nuclear and cytosolic protein with the monosaccharide n-acetyl glucoseamine on serine or threonine residues. This modification resembles and can compete with phosphorylation on same or adjacent serine and threonine residues and thus may affect their activity. In this respect: We are focusing in this unique proteines modification and its prevalence on nuclear and cytosolic protein in the human colorectal adenocarcinoma and the murine luwis lung carcinoma. The role of O-GlcNAc post translational modification during cancer development and metastasis.
- Although many proteins involved in a variety of cellular functions and diseases were found to be O- GlcNAcylated, the role of
- O- GlcNAcylation in the development of cancer is yet unknown. Still, this PTM is known as a neutrient sensor and as a regulator of insulin signaling. Recently, we discovered that O- GlcNAcylation is elevated in SW620 metastatic colorectal cancer clone compared to its SW480 primary clone. This elevation coincides with lower expression of the enzyme O -GlcNAcase (OGA) — which removes
- O -GlcNAc — in the metastatic cells. This finding suggests that O -GlcNAcylation is significantly altered upon the transformation of tumor cells towards metastasis. Our aims are to elucidate the role of O -GlcNAcylation in tumor malignancy and metastasis. Towards this goal, the proliferative, apoptotic and metastatic phenotypes of siOGA human colorectal cancer cells are under in vitro and in vivo invistigation Identification of O- GlcNAcylated proteins involved in specific cellular processes and elucidating their role in neoplastic development and cancer progression, may contribute for the understanding of colorectal cancer etiology. This would be most valuable for the development of new strategies for the prevention and treatment of colorectal cancer. The effect of O-GlcNAcylation on hnRNP A1 function with respect to cancer development and metastasis.
- The hnRNPs are a family of key proteins involved gene expression at both the transcriptional and translational levels. To fulfill their function, hnRNPs contain RNA recognition motifs and nuclear localization signal. The hnRNP A1 isoform is involved in mRNA transport to the cytoplasm, and phosphorylation of hnRNP A1 affects its accumulation in the cytoplasm. Our resultsshow that serine and/or threonine residues of hnRNP A1 are modified by O -GlcNAc. Although glycosylation is believed to act as a nuclear import signal, its role in hnRNP A1 translocation is yet to be elucidated. The hnRNPs are thought to increase the survival and proliferation rate of cancer cells. Indeed, the expression level of hnRNP A1 was found to be elevated in proliferating cells. Elucidating the influence of modifications in hnRNP A1 on its function and regulation in the development and invasion capacity of neoplastic cells could thus advance cancer research. This project is aiming to characterize the nature and specification of hnRNP A1 expressed in colorectal cancer clones and to identify its O-GlcNAcylation site(s) and to investigate the role of these sites in hnRNP A1 translocation and regulation, and thereby in its functions in cancer cell proliferation and apoptosis. Revealing sites of O-GlcNAcylation and their effects on the function of hnRNP A1 will significantly contribute to the understanding of the role of this protein and its modifications in neoplasia. The role of N-glycosylation on lipoprotein interactions and receptor mediated endocytosis.
- Lipoprotein mediated endocytosis is crucial for nutrition, reproduction, immunity and thus survival of organisms throughout the animal kingdom. This study is aiming to investigate the specific interaction between the ligand and its receptor. Two crustacean hemolymphatic lipoproteins, the major yolk protein precursor vitellogenin and a newly discovered discoidal lipoprotein, representing reproductive dependent and independent model ligands, respectively, are under invesitgation. Specifically, the role of N -glycosylation of the ligand in the interaction with the receptor is of specific interest. This study is the first to investigate glycosylation as a possible mediator of ligand-receptor interaction and ligand specificity, particularly the role of glycan moieties in uptake of hemolymphatic lipoproteins. This novel aspect of ligand-receptor interactions bears possible insights into new models of nutrition delivery, immunity and invertebrate pest management and control.