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 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.
Publications and presentaions from last year
Abraham M., Klein S., Bulvik B., Wald H., Weiss ID., Olam D., Weiss L., Beider K., Eizenberg O., Wald O., Galun E., Avigdor A., Benjamini O., Nagler A., Pereg Y., Tavor S., Peled A (2017). The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia 31:2336-46.
Abraham M., Pereg Y., Bulvik B., Klein S., Mishalian I., Wald H., Eizenberg O., Beider K., Nagler A., Golan R., Vainstein A., Aharon A., Galun E., Caraco Y., Or R., Peled A (2017). Single dose of the CXCR4 antagonist BL-8040 induces a rapid, robust mobilization and collection of human CD34+ cells in healthy volunteers. Clin Cancer Res. 23:6790-6801.
Klein S., Abraham M., Bulvik B., Dery E., Weiss ID., Barashi N., Abramovitch R., Wald H., Tavor S., Olam D., Weiss L., Beider K., Eizenberg O., Wald O., Galun E., Avigdor A., Benjamini O., Nagler A., Pereg Y., Peled A (2018). CXCR4 promotes neuroblastoma tumor growth and resistance to therapy by regulating ERK and BCL-2 and cyclin-D1 via altered miR-15a/16-1 expression. Cancer Res. 15;78(6):1471-1483.
Ella E., Harel Y., Abraham M., Wald H., Benny O., Karsch-Bluman A., Dive V., Devel L., Izhar U., Shapira OM., Yoon D., Lee HS., Sugarbaker DJ., Burt B., Peled A., Wald O (2018). Matrix metalloproteinase 12 (MMP-12) promotes tumor propagation in the lung. J Thorac Cardiovasc Surg. 155(5):2164-2175.
Abraham M., Karni A., Mausner-Fainberg K., Weiss ID., Peled A (2017). Natural and induced immunization against CCL20 ameliorate experimental autoimmune encephalitis and may confer protection against multiple sclerosis. Clin Immunol. 183:316-24.
Abraham M., Wald H., Vaizel-Ohayon D., Grabovsky V., Oren Z., Karni A., Weiss L., Galun E., Peled A., Eizenberg O (2017). Development of novel promiscuous anti-chemokine peptibodies for treating autoimmunity and inflammation. Front Immunol. 8:1432.
Peled A., Nagler A (2017). NK cell destiny after HaploSCT with PTCy (commentary). Blood. 131(2):161-162.
Michal Abraham et al. Two Oral presentations at the ASH in 2016 and 2017 on Leukemia and stem cell mobilization.
Productivity in Nature as well as in Biomedical Sciences is dependent on personality (innovative, hardworking, professionalism, knowledge, curiosity, stamina and love to science and good food). We educate to this in our lab and institute.
The most valuable and important asset of any scientific team is the students and their ability to cook good food and have fun together.