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Research Interests

I am an associate professor at the Gene Therapy Institute, Hadassah Medical Center, Jerusalem where I directs a laboratory, focusing on the role of chemokines and chemokine receptor in stem cell mobilization, inflammation and cancer. My laboratory devlop novel cell and molecular therapeutics for cancer and have been involved in the last 16 years in the development of novel therapies to cancer that are currently in Phase II and III clinical studies. Our laboratory worked in close collaboration with Israeli Biotechnology companies such as Biokine Therapeutics LTD, BiolineRX, and Gamida Cell.
 
 
Proposed MOA
Proposed Mechanism Of Action (MOA) of how the chemokine receptor CXCR4 promotes neuroblastoma tumor growth and resistance to therapy. Cancer Res. 15;78(6):1471-1483.
(A) Activation of CXCR4 by overexpression of the receptor induces two important separate signaling pathways. On the one hand, there is an upregulation of miR-15a/16-1 leading to the downregulation of target genes such as BCL-2 and CCND1. On the other hand, the MAPK signaling cascade is activated. This process shifts the cells dependency leading to the oncogenic addiction on CXCR4 resulting in enhanced cell survival. (B) In the case of inhibition of CXCR4 by inhibitors such as BL-8040, miR-15a/16-1 are upregulated leading to reduction in BCL-2 and CCND1 survival signals. Nonetheless, MAPK signaling pathway is repressed leading to cell death.

 

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