פרופ' רונית סצ'י-פאינרו עוסקת בחקר הסרטן בפקולטה לרפואה ע"ש סאקלר.
פרופ' רונית סצ'י-פאינרו
מופקד על קתדרה בדיקאנט ומנהל הפקולטה לרפואה
ראש מרכז בדיקאנט ומנהל הפקולטה לרפואה
ועדת מינויים יחידתית בפיזיולוגיה ופרמקולוגיה
מידע כללי
Biography
Education
1999 | Ph.D. University of London, Faculty of Medicine, School of Pharmacy, UK. Thesis title: “PDEPT: Polymer Directed Enzyme Prodrug Therapy”. PI: Ruth Duncan.
1996 | Internship in Industrial Pharmacy, Perio Products LTD, Jerusalem, Israel.
1995 | B.Pharm. The Hebrew University Jerusalem, Israel.
Research
Angiogenic Switch Using Rationally-Designed Theranostic Nanomedicines
Our research interests include investigations related to tumor biology, tumor dormancy, mechanism of action of angiogenesis inhibitors, self-assembly of polymeric architectures and novel approaches to target cancer. Throughout, we have maintained an interest in understanding the biological rationale for the design of polymer therapeutics suitable for transfer into clinical testing. Our primary interests are the molecular basis of tumor angiogenesis and the rational design of polymer therapeutics. Our research includes identification and characterization of genes and microRNAs associated with the switch from a dormant avascular tumor phenotype to a fast-growing angiogenic tumor in human cancers and their corresponding mouse models. We focus on the design and characterization of novel drug delivery platforms, including dendrimers and hyperbranched polymer–based nanoparticles, and the design of highly-selective targeting molecules integrating biology, chemistry, protein engineering, computational approaches, material sciences and nanotechnology to selectively guide drugs into pathological sites. Our vision is that novel approaches to target anticancer, anti-angiogenic drugs, miRNA and siRNAs to endothelial and tumor cells to potentially treat angiogenesis-dependent diseases could transform cancer into a chronically-manageable disease.
Research methods used include sequencing, gene cloning, quantitative RT-PCR, immunofluorescence, cell culture, scanning electron microscopy, mass spectrometry, NMR, HPLC, in situ hybridization, bioinformatics, polymer chemistry, molecular imaging, angiogenesis assays, animal models of cancer (human xenografts in mice, syngeneic and transgenic mice models), pharmacokinetics and pharmacodynamics.
Publications
Satchi-Fainaro R*, Ferber S*, Segal E, Ma L, Dixit N, Ijaz A, Hlatky L, Abdollahi A, Almog A, Prospective identification of glioblastoma cells generating dormant tumors, PLoS One, 7: e44395. (2012).
Herzog IM, Green KD, Berkov-Zrihen Y, Feldman M, Vidavski RR, Eldar-Boock A, Satchi-Fainaro R, Eldar A, Garneau-Tsodikova S and Fridman M, 6"-Thioether tobramycin analogues: Towards selective targeting of bacterial membranes, Angewandte Chemie, 51, 5652-5656 (2012).
Benayoun L, Gingis-Velitski S, Voloshin T, Segal E, Segev R, Munster M, Bril R, Satchi-Fainaro R, Scherer SJ, Shaked Y, Tumor-initiating cells of various tumor types exhibit differential angiogenic properties and react differently to antiangiogenic drugs, Stem Cells -Cancer Stem Cells, 30, 1831-41 (2012).
Benayoun L, Schaffer M, Brill R, Gingis-Velitski S, Segal E, Nevelsky A, Satchi-Fainaro R, Shaked Y, Porfimer-sodium (Photofrin-II) in combination with ionizing radiation inhibits tumor initiating cell proliferation and improves glioblastoma treatment efficacy, Cancer Biology & Therapy, 31;14 (2012). (Cover feature).
Miller K, Clementi C, Polyak D, Eldar-Boock A, Benayoun L, Barshack I, Shaked Y, Pasut G and Satchi-Fainaro R, Anti-angiogenic activity of polyethyleneglycol-based paclitaxel and alendronate for the treatment of breast cancer bone metastases, Biomaterials, 34: 3795–3806 (2013).
Chuderland D, Ben-Ami I, Kaplan-Kraicer R, Grossman H, Komsky A, Satchi-Fainaro R, Eldar-Boock A, Ron-El R, Shalgi R, Hormonal regulation of pigment epithelium derived factor (PEDF) in granulosa cells, Molecular Human Reproduction, 19, 72-81 (2013).
Ferber S, Tiram G and Satchi-Fainaro R, Evaluation of microvessels density, morphology and functionality in matrigel plugs by non-invasive intravital microscopy, The Journal of Visualized Experiments (JoVE), in press (2014).
Redy O, Kisin-Finfer E, Shiran Ferber, Satchi-Fainaro R*, and Shabat D*, Synthesis and use of qcy7-derived modular probes for detection and imaging of biologically relevant analytes, Nature Protocols, 9:27-36 (2014). *Corresponding authors
Kisin-Finfer E, Ferber S, Blau R, Satchi-Fainaro R, Shabat D, Synthesis and evaluation of new NIR-fluorescent probes for cathepsin B: ICT versus FRET as a turn-ON mode-of-action, Bioorganic and Medicinal Chemistry Letters, 24:2453-8 (2014).
Ferber S, Baabur-Cohen H, Blau R, Epshtein Y and Satchi-Fainaro R, Nanomedicines for personalized theranostics of angiogenesis-dependent diseases, Cancer Letters, in press (2014).
Eldar-Boock A, Ryppa C, Sanchis J, Baabur-Cohen H, Many A, Vicent MJ, Kratz F, Satchi-Fainaro R, Integrin-targeted nano-sized polymeric systems for paclitaxel: A comparative study, Polymers for Advanced Technologies, in press (2014).
Markovsky E, Baabur-Cohen H, Satchi-Fainaro R, Anticancer polymeric nanomedicine bearing synergistic drug combination is superior to a mixture of individually-conjugated drugs, Journal of Controlled Release, in press (2014).
Redy-Keisar O, Ferber S, Satchi-Fainaro R* and Shabat D*, NIR Fluorogenic Dye as a Modular Platform for Prodrug Assembly: Real-Time in vivo Monitoring of Drug Release, ChemMedChem, 10(6): 999-1007 (2015). *Corresponding authors.
Scomparin A, Salmaso S, Eldar-Boock A, Ben- Shushan D, Ferber S, Tiram G, Shmeeda H, Landa-Rouben N, Leor J, Caliceti P, Gabizon A, Satchi-Fainaro R, A comparative study of folate receptor-targeted doxorubicin delivery systems: dosing regimens and therapeutic index, Journal of Controlled Release, 208 106-120 (2015).
Bonzi G, Salmaso S, Scomparin A, Eldar-Boock A, Satchi-Fainaro R, Caliceti P, A novel pullulan bioconjugate for selective breast cancer bone metastases treatment, Bioconjugate Chemistry 26(3):489-501 (2015).
Tiram G, Segal E, Krivitsky A, Shreberk-Hassidim R, Ferber S, Ofek P, Udagawa T, Edry L, Shomron N, Roniger M, Kerem B, Shaked Y, Aviel-Ronen S, Barshack I, Calderón M, Haag R and Satchi-Fainaro R, Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma-Targeted Dendritic Polyglycerol Nanopolyplexes, ACS Nano 10(2): 2028-2045 (2016).
Fisusi FA, Siew A, Chooi KW, Okubanjo O, Garrett N, Lalatsa K, Serrano D, Summers I, Moger J, Stapleton P, Satchi-Fainaro R, Schätzlein AG, Uchegbu IF, Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels – A Strategy for Brain Cancer Treatments, Pharmaceutical Research 33 (5), 1289-1303 (2016).
Schwartz H, Blacher E, Amer M, Livneh N, Abramovitz L, Klein A, Ben-Shushan D, Soffer S, Blazquez R, Barrantes-Freer A, Müller M, Müller-Decker K, Stein R, Tsarfaty G, Satchi-Fainaro R, Umansky V, Pukrop T, Erez N, Incipient melanoma brain metastases instigate astrogliosis and neuroinflammation, Cancer Research, DOI: 10.1158/0008-5472.CAN-16-0485 (2016).
Golan M, Feinshtein V, Polyak D, Scomparin A, Satchi-Fainaro R, David A, Inhibition of gene expression and cancer cell migration by CD44v3/6- targeted polyion complexes, Bioconjugate chemistry 27 (4), 947-960 (2016).
Ofek P, Calderón M, Sheikhi Mehrabadi F, Krivitsky A, Ferber S, Tiram G, Yerushalmi N, Kredo-Russo S, Grossman R, Ram Z, Haag R, Satchi-Fainaro R, Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex, Nanomedicine: Nanotechnology, Biology and Medicine, pii: S1549-9634(16)30063-6. doi: 10.1016 (2016).
Polyak D, Krivitsky A, Scomparin A, Eliyahu S, Kalinski H, Avkin-Nachum S, Satchi-Fainaro R, Systemic delivery of siRNA by aminated poly(α) glutamate for the treatment of solid tumors, Journal of Controlled Release, 257:132-142 (2017).
Baabur-Cohen H, Vossen L, Rune Krüger H, Eldar-boock A, Yeini E, Landa-Rouben N, Tiram G, Wedepohl S, Markovsky E, Leor J, Calderón M and Satchi-Fainaro R, In vivo comparative study of distinct polymeric architectures bearing a combination of paclitaxel and doxorubicin at a synergistic ratio, Journal of Controlled Release, 257:118-131 (2017).
Krivitsky A, Polyak D, Scomparin A, Eliyahu S, Ori A, Avkin Nachum S, Krivitsky V, Satchi-Fainaro R. Structure-function correlation of aminated poly(α) glutamate as siRNA nanocarriers. Biomacromolecules. 17:2787-2800 (2016).
Shatsberg Z, Zhang X, Ofek P, Malhotra S, Krivitsky A, Scomparin A, Tiram G, Calderón M, Haag R, Satchi-Fainaro R. Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy, Journal of Controlled Release, 239:159-68 (2016).
Gnaim S, Scomparin A, Li X, Baran PS, Rader C, Satchi-Fainaro R, Shabat D. Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct C-H Functionalization of Bioactive Heteroarenes, Bioconjugate Chemistry, 27:1965- 71 (2016).
Hananya N, Eldar-Boock A, Bauer CR, Satchi- Fainaro R, Shabat D, Remarkable Enhancement of Chemiluminescent Signal by Dioxetane Fluorophore Conjugates: Turn-ON Chemiluminescence Probes with Color Modulation for Sensing and Imaging, Journal of the American Chemical Society (JACS). 138):13438-13446 (2016).
Alishekevitz D, Gingis-Velitski S, Kaidar-Person O, Gutter-Kapon L, Scherer SD, Raviv Z, Merquiol E, Ben-Nun Y, Miller V, Rachman-Tzemah C, Timaner M, Mumblat Y, Ilan N, Loven D, Hershkovitz D, Satchi-Fainaro R, Blum G, P Sleeman J, Vlodavsky I, Shaked Y, Macrophage-Induced Lymphangiogenesis and Metastasis following Paclitaxel Chemotherapy Is Regulated by VEGFR3, Cell Reports 17:1344-1356 (2016).
Markovsky E, Eldar-Boock A, Ben-Shushan D, Baabur-Cohen H, Yeini E, Many A, Pisarevsky E, Aviel-Ronen S, Barshack I, Satchi-Fainaro R, Targeting NCAM-expressing neuroblastoma with polymeric precision nanomedicine, Journal of Controlled Release, 249:162-172 (2017).
Zupančič E, Curato C, Paisana M, Rodrigues C, Porat Z, Viana AS, Afonso CAM, Pinto J, Gaspar R, Moreira JN, Satchi-Fainaro R, Jung S, Florindo HF, Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming. Journal of Controlled Release, 258:182-195 (2017).
Ferguson EL, Scomparin A, Hailu H, Satchi- Fainaro R. HPMA Copolymer-phospholipase and Dextrin-Phospholipase A2 as Model Triggers for Polymer Enzyme Liposome Therapy (PELT). Journal of Drug Targeting, Jul 21:1-33. doi: 10.1080/1061186X.2017.1358726 (2017).
Markovsky E*, Vax E*, Ben-Shushan D, Eldar- Boock A, Shukrun R, Yeini E, Barshack I, Caspi R, Harari-Steinberg O, Pode-Shakked N, Dekel B, Satchi-Fainaro R, Wilms' tumor NCAM-expressing cancer stem cells as potential therapeutic target for polymeric nanomedicine, Molecular Cancer Therapeutics, Jul 20. pii: molcanther.0184.2017. doi: 10.1158/1535-7163.MCT-17-0184 (2017).
Eldar-Boock A, Blau R, Ryppa C, Baabur-Cohen H, Many A, Vicent MJ, Kratz F, Sanchis J, Satchi-Fainaro R. Integrin-Targeted Nano-Sized Polymeric Systems for Paclitaxel Conjugation: A Comparative Study. Journal of Drug Targeting. 8:1-16 (2017).
Hananya N, Green O, Blau R, Satchi-Fainaro R*, Shabat D*, Highly-Efficient Chemiluminescence Probe for Detection of Singlet Oxygen in Living Cells. Angewandte Chemie Int Ed Engl., Jul 27. doi: 10.1002/anie.201705803 (2017). Co-Corresponding authors.
Reviews
Markovsky E, Baabur-Cohen H, Eldar-Boock A, Omer L, Tiram G, Ferber S, Ofek P, Polyak D, Scomparin A and Satchi-Fainaro R, Administration, distribution, metabolism and elimination of polymer therapeutics, Theme issue: Drug Delivery Research in Europe, Journal of Controlled Release, 161, 446–460 (2012).
Eldar-Boock A*, Polyak D*, Scomparin A, Satchi-Fainaro R, Nano-sized polymers and liposomes designed to deliver combination therapy for cancer, Current Opinion in Biotechnology, 24: 682–689 (2013).
Ferber S, Tiram G and Satchi-Fainaro R, Targeting Drugs to Cancer: A Tough Journey to the Tumor Cell, In Cancer Targeted Drug Delivery: An Elusive Dream, Eds. Han Bae Y, Mrsny R and Park K, Springer Science and Business Media, New York, Part V, pp 509-542 (2013).
Scomparin A*, Tiram G*, Satchi-Fainaro R, Nanoscale-Based Delivery of RNAi for Cancer Therapy, Erdmann VA and Barciszewski J (Eds.), In: DNA and RNA Nanobiotechnologies in Medicine: Diagnosis and Treatment of Diseases, RNA Technologies, Springer-Verlag Berlin Heidelberg, 349-372 (2013)
Polyak D*, Eldar-Boock A*, Baabur-Cohen H and Satchi-Fainaro R, Polymer conjugates for focal and targeted delivery of drugs, Polymers for Advanced Technologies, 24, 777–790 (2013).
Ofek P, Tiram G, Satchi-Fainaro R, RNAi Antiangiogenic Nanomedicines, Advanced Drug Delivery Reviews, in press (2014).
Tiram G, Scomparin A, Ofek P and Satchi-Fainaro R, Interfering cancer with polymeric siRNA nanocarriers, Journal of Biomedical Nanotechnology, 10, 50-66 (2014).
Ben-Shushan D*, Markovsky E*, Gibori H*, Tiram G, Scomparin A, Satchi-Fainaro R, Overcoming obstacles in microRNA delivery towards improved cancer therapy, Drug Delivery and Translational Research, 4, 38-49 (2014).
Tiram G, Scomparin A, Ofek P and Satchi-Fainaro R, Interfering cancer with polymeric siRNA nanocarriers, Journal of Biomedical Nanotechnology, 10, 50-66 (2014).
Scomparin A, Polyak D, Krivitsky A, Satchi Fainaro R, Achieving successful delivery of oligonucleotides- From physico-chemical characterization to in vivo evaluation, Biotechnology Advances, 33 (6pt3) 1294-1309 (2015).
Blau R, Krivitsky A, Epshtein Y, Satchi-Fainaro R, Are nanotheranostics and nanodiagnostics-guided drug delivery stepping stones toward precision medicine? Drug Resistance Updates, in press (2016).
Ofek P, Tiram G, Satchi-Fainaro R, RNAi Antiangiogenic Nanomedicines, Advanced Drug Delivery Reviews, in press (2016).
Blau R, Krivitsky A, Epshtein Y, Satchi-Fainaro R. Are nanotheranostics and nanodiagnostics-guided drug delivery stepping stones towards precision medicine? Drug Resistance Updates, 27:39-58 (2016).
Ofek P, Tiram G, Satchi-Fainaro R. Angiogenesis regulation by nanocarriers bearing RNA interference. Advanced Drug Delivery Reviews, in press (2017).
Blau R, Neeman M, Satchi-Fainaro R, Emerging nanomedical solutions for angiogenesis regulation, Advanced Drug Delivery Reviews, in press (2017).
Scomparin A, Florindo HF, Tiram G, Satchi-Fainaro R, Two-step polymer- and liposome- enzyme pro-drug therapies for cancer: PDEPT and PELT concepts and future perspectives, Advanced Drug Delivery Reviews, in press (2017).
Satchi-Fainaro R, Vicent MJ, Richardson S, Editorial- Professor Ruth Duncan Coined the Term Polymer Therapeutics, Journal of Drug Targeting, in press (2017).