BAR-ILAN INSTITUTE OF NANOTECHNOLOGY & ADVANCED MATERIALS | 2019 ANNUAL REPORT

53 Prof. David Cahen Department of Chemistry BIU Faculty of Chemistry WIS Member of BINA, Nano-Energy Center Research Areas • Alternative Energy: Photovoltaics (PV), esp. materials for high voltage, low-cost, stable PV • Combinatorial synthesis and characterization of optoelectronic materials • Semiconductor materials & device chemistry & physics • Biomolecular optoelectronics Fundamentals of proteins as electronic materials Abstract The Cahen-Zaban group studies (opto) electronic materials, esp. for Photovoltaics. A major tool is combinatorial material science to answer renewable energy’s need for new materials, i.e., to explore compounds with unique characteristics with current focus on halide perovskites and charge-selective metal oxides. Further interests are in Biomolecules, esp. proteins as electronic materials for future bioelectronics. renew, exhibit multi-lineage differentiation potential and the generation of xenografts that recapitulate the parental tumor. GSCs are resistant to conventional therapies as compared with differentiated tumor cells, and therefore remain at the tumor site following resection, which eventually leads to tumor recurrence. Therefore, delineating the cellular and molecular mechanisms that control the stemness and functions of GSCs is essential for identifying therapeutic approaches to selectively target GSCs. We have been demonstrated the role of autophagy in determining the radiation resistance of GSCs and identified specific signaling pathways such as the miR-137- RTVP-1-CXCR4 pathway and the RasGEF, RasGRP3 in controlling the stemness and migration of GSCs. In addition to glioma, we have also established cancer stem cells frommeningioma and brain metastases from lung and breast tumors. For all these tumors we currently have neurospheres, organoids and patient derived xenografts (PDX). WE are employing these models for studying the role of novel non-coding RNAs in the biology of these cells and in their cross-interaction with microglia via exosomal delivery. Abstract Topic 2 Exosomes in intercellular communication and drug delivery and therapeutics Exosomes are small vesicles released by all cells in the body and play major roles in intercellular interaction. Exosomes can be isolated from serum and plasma (in addition to almost every body’s fluid) and serve as important source for circulating biomarkers. Exosomes carry a very heterogeneous cargo that in many cases reflects the nature and status of the secreting cells. Therefore, exosomes can be employed to analyze disease status is a tissue-dependent manner and response of various cells to different therapies. In addition, exosomes can be employed to deliver different therapeutics such as proteins, RNA molecules and oncolytic viruses. We have developed novel approaches to track exosomes and their cargo in vitro and in vivo and exosomes targeted to specific cells and tissues and demonstrated therapeutic impact in a number of pre-clinical models. Abstract Topic 3 Human in vitro models of neurological disorders We have generated various immortalized human cells including neural stem cells (NSCs), astrocytes, microglia, oligodendrocytes, and neurons that maintain the phenotypes and functions of the original cells. Using CRISPR/Cas9 we can generate various models of neurological diseases and study disease mechanisms and neuron-glia cell interactions. Moreover, we have developed an array of reporters that allow us to analyze cell differentiation, fate and signaling pathways in pathological conditions and in response to various treatments. Abstract Topic 4 Collaboration with BioIncept LLC We are actively collaborating with BioIncept on the protective effects of a peptide sPIF from acute radiation syndrome (ARS) and in other studies related to the effects of sPIF in neurological disorders and Duchenne muscular dystrophy. In addition, we have been studying the effects of sPIF on glioma cells and cancer stem cells derived from brain metastases. Publications 2018 and 2019 • Morgoulis D., Berenstein P., Cazacu S. et al., “sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/ let-7 and miR-21 pathways”, Cell Death Dis 10, 82, 2019 . • Hayrabedyan S., Shainer R., Yekhtin Z. et al., “Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice”, Sci Rep 9, 12876, 2019 . • Bier et al., “Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy,” Biomaterials, 2018 . • A Korkut, S Zaidi, RS Kanchi, S Rao, NR Gough, A Schultz, X Li, ..., “A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF- Є Superfamily”, Cell systems 7 (4), 422-437. e7, 1, 2018 . • S Cazacu, W Jiang, H Zane, S Kalkanis, C Brodie, “Novel in vitro and in vivo models for studying brain metastasis and tumor- microenvironment interactions.”, Cancer Research 78 (10), 65-66, 2018 .