| 72 | 2024 Annual Report Prof. Nir Uri The Mina & Everard Goodman Faculty of Life Sciences Targeting Selectively the Energy Generation System of Cancer Cells Research Areas • Molecular biology of cancer • Intracellular tyrosine kinase Fer • TMF/ARA160 Abstract The aspiration to achieve efficacious cancer-targeted therapy involves intense global R&D efforts. Blockage of fundamental processes like malignant cells' unique and reprogramed energy generation system should offer new tools for efficient interference with cancer progression. While deciphering the energy generation system of cancer cells, we identified an enzyme termed- FerT, which normally resides only in the energy power station (termed mitochondria) of sperm cells and is harnessed by cancer cells to empower their reprogrammed mitochondria. We found that FerT potentiates energy generation by mitochondria in cancer cells in general and in metastatic cells (cells that leave the primary tumor and are spreading throughout the patient's body) in particular, thereby enabling them to survive under stress conditions like nutrient and oxygen deprivation. This supports the survival of metastatic cancer cells under harsh conditions encountered during dissemination throughout the patient's body. To translate these findings into a novel anti-cancer therapy, we have combined synthetic chemistry, robotic, and high throughput screening approaches to develop a synthetic low molecular weight compound that binds and inhibits the activity of the FerT enzyme. Our lead compound called E260 targets and inhibits FerT in the power station- mitochondria of malignant cells, thereby selectively imposing energy crisis and consequent death of cancer cells in general and metastatic cells in particular. Since the metastatic spreading of malignant cells throughout the patient's body is the leading cause of death from cancer, our findings portray E260 as a new, potential, and promising anti-cancer drug. The above-described findings were published in the high-profile journal Nature communication: Elkis, Y., Cohen, M., Yaffe, E., Feldman, T., Satmary, S., Nyska, A., Shpungin, S., and Nir, U. (2017) A Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells. Nature Comm. DOI:10.1038/s41467-017-00832-w Deformation and destruction of the mitochondria (energy power station) of metastatic cancer cells (indicated by blue arrows on the right panels representing two magnifications) by the newly developed anti-cancer agent E260. Publications 2023 and 2024 • George Abdo, Uri Nir, Rasha Rawajdey, Wadie Abu Dahoud, Jammal Massalha, Taleb Hajouj, Mohammad H Assadi, Nseir William. “A Novel Score-Based Approach by Using Routine Laboratory Tests for Accurate Diagnosis of Spontaneous Bacterial Peritonitis (SBP) in Cirrhotic Patients.” EJIFCC, 2023. • Uri Nir, Elina Grinshtain, Haim Breitbart. “Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells.” International Journal of Molecular Sciences, 2023. Prof. Noked Malachi Department of Chemistry Functional Thin Film for Electrochemical Devices Research Areas Surface-directed chemical reaction in vacuum (atomic/molecular layer deposition ALD/MLD) for: • Stabilization of battery electrodes in implanted medical devices • Designing arrays of nano-materials with controlled morphology and structure for electrochemical devices • Modified metallic anode surfaces for next-generation rechargeable batteries Abstract Our laboratory utilizes state-of-theart synthesis techniques for interfacial modification of electrochemically active surfaces using functional thin films. Students in our lab experience synthesis through surface-directed chemical reactions in a vacuum (atomic/molecular layer deposition ALD/MLD) and in carefully chosen electrolyte solutions (surfacedirected electrodeposition). The characterization of the synthesized thin films and the fundamental studies of their efficacy as surface modification materials are conducted using state-ofthe-art microscopic and spectroscopic surface analysis facilities available at Bar-Ilan University and currently being constructed in our lab.
RkJQdWJsaXNoZXIy NDU2MA==