Fax :
erica.salvati@cnr.it
Researcher
Istitute of Molecular Biology and Pathology - National Research Council
Department of Biology and Biotecnology - Charles Darwin
Sapienza University of Rome - \DNA\/RNA open lab\ 3\u00b0 piano, Via degli Apuli 4 00185 Roma
My research activities in the last years have been focused in the telomere maintenance mechanisms in cancer cells. I started by studying the mechanisms of action of G-quadruplex ligands: cell permeable small molecules able to bind and stabilize the guanine-rich 3'-overhang of human telomeres. G-quadruplex stabilization were shown to lead to telomere's nucleo-protein architecture disruption, induction of a DNA damage response activation and eventually apoptosis. The comprehension of the effects of G-quadruplex stabilization in human cancer cells and in animal models, highlighted the potential application of these molecules in anti-cancer therapy as single agents and in combination with standard chemotherapics. Indeed they also revealed new functions of quadruplex DNA structures in different processes as DNA replication and transcription. This has led me to develop my ongoing project concerning the study of telomere replication in cancer cells to find molecular determinants of sensitivity to targeted therapy. In addition, I have focused my attention on a particular subclass of tumors that do not express the Telomerase enzyme as a telomere lenghtening mechanisms, but relies on alternative mechanisms (ALT) based on homologous recombination and homology directed DNA replication. ALT mechanisms are expessed in very aggressive tumors of mesenchymal origin (i.e. gliomas and sarcomas) with poor therapeutic options. In this regard, my actual project aims at determining the presence of ALT mechanisms in human sarcoma samples, and their correlation with the mutational status of other oncogenes/oncosuppressors, and with clinical data (prognosis, response to treatments) and at testing sensitivity of ALT vs Telomerase positive tumors to different anti-cancer pharmacological treatments.
|
1. Pompili L, Leonetti C, Biroccio A, Salvati E. Diagnosis and treatment of ALT tumors: is Trabectedin a new therapeutic option? J Exp Clin Cancer Res. 2017 Dec 22;36(1):189. Review.
2. Salvati E, Botta L, Amato J, Di Leva FS, Zizza P, Gioiello A, Pagano B, Graziani G, Tarsounas M, Randazzo A, Novellino E, Biroccio A, Cosconati S. Lead Discovery of Dual G-Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases (PARPs) Inhibitors: A New Avenue in Anticancer Treatment. J Med Chem. 2017 May 1
3. Salvati E, Doria F, Manoli F, D'Angelo C, Biroccio A, Freccero M, Manet I. A bimodal fluorescent and photocytotoxic naphthalene diimide for theranostic applications. Org Biomol Chem. 2016 Jul 26;14(30):7238-49
4. Salvati E, Rizzo A, Iachettini S, Zizza P, Cingolani C, D'Angelo C, Porru M, Mondello C, Aiello A, Farsetti A, Gilson E, Leonetti C, Biroccio A. A basal level of DNA damage and telomere deprotection increases the sensitivity of cancer cells to G-quadruplex interactive compounds. Nucleic Acids Res. 2015 Feb 18;43(3):1759-69.
5. Salvati E, Zizza P, Rizzo A, Iachettini S, Cingolani C, D’Angelo C, Porru M, Randazzo A, Pagano B, Novellino E, Pisanu ME, Stoppacciaro A, Spinella F, Bagnato A, Gilson E, Leonetti C, and Biroccio, A. Evidence for G-quadruplex in the promoter of vegfr-2 and its targeting to inhibit tumor angiogenesis. Nucleic Acids Res. 2014 Mar;42(5):2945-57.
6. Iachettini S, Stevens MFG, Mark Frigerio, Hummersone MG, Hutchinson I, Garner TP, Searle S, Wilson DW, Munde M, Nanjunda R, D’Angelo C, Zizza P, Rizzo A, Cingolani C, De Cicco F, Porru M, D’Incalci M, Leonetti C, Biroccio A, Salvati E. On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts. Journal of Experimental & Clinical Cancer Research 2013, 32:68 (19 September 2013).
7. Rizzo A, Salvati E, Biroccio A. Methods of studying telomere damage induced by quadruplex-ligand complexes. Methods. 2012 May;57(1):93-9. doi: 10.1016/j.ymeth.2012.02.010. Epub 2012 Mar 4. Review.
8. Salvati E, Scarsella M, Porru M, Rizzo A, Iachettini S, Tentori L, Graziani G, D'Incalci M, Stevens MF, Orlandi A, Passeri D, Gilson E, Zupi G, Leonetti C, Biroccio A. PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy. Oncogene. 2010 Nov 25;29(47):6280-93. Epub 2010 Aug 30.
9. Salvati E., Leonetti C., Rizzo A., Scarsella M., Mottolese M., Galati R., Sperduti I., Stevens M., D’Incalci M., Blasco M., Chiorino G., Horard B., Gilson E., Zupi G. and Biroccio A.: Telomere damage promotes antitumoral activity of the G-quadruplex ligand RHPS4. JCI. 2007 Nov;117(11):3236-47.
|
| Carmen Maresca (Technician) Valentina Piani (Student) |
Stefano Cacchione, Sapienza
Antonella Sgura, Roma Tre
Grazia Graziani, Tor Vergata
Annamaria Biroccio, IFO-IRCCS Istituto Nazionale dei Tumori Regina Elena
|
Personal Information Date and place of birth: Rome, June 3rd 1975 Work address: IBPM Institute of Molecular Biology and Pathology CNR National Research Council of Italy c/o Department of Biology and Biotechnology Sapienza University Via degli Apuli 4 00185 Rome, Italy
Education · Specialist in Clinical Biochemistry at the University of Rome "Tor Vergata", Italy, 2007. · PhD in Cellular and Molecular Biology at the University of Rome "Tor Vergata", Italy, 2004. · Degree in Biological Sciences at the University of Rome “La Sapienza”, Italy, 2000.
Scientific and professional experiences • November 2018-present: Researcher in staff at IBPM Institute of Molecular Biology and Pathology- CNR National Research Council of Italy. • June 2016-November 2018: Recipient of research fellow as Principal Investigator within the Grant from Italian Association for Cancer Research MFAG 2015-2019. • June 2015-May 2016: Recipient of research fellow as Post-doc researcher at the Oncogenomic and Epigenetic Unit of Regina Elena National Cancer Institute, Rome. Supervisor Dr. Annamaria Biroccio • June 2014-May 2015: Recipient of 12-months research scholarship within the Grant “Post-Doctoral Fellowship-year 2015” funded by Fondazione Veronesi. • January 2012-May 2014: Recipient of research fellow as Post-doc researcher at the Oncogenomic and Epigenetic Unit of Regina Elena National Cancer Institute. Supervisor Dr. Annamaria Biroccio • Jauary 2009-December 2011: Recipient of a three-year FIRC fellowship at the Laboratory of Experimental Chemotherapy, Regina Elena Cancer Institute, Rome. Supervisor: Dr Gabriella Zupi. • January 2007-December 2009: Recipient of a CNRS Post-doc fellowship at the Ecole National Supériéure, Lyon. Supervisor: Prof. Eric Gilson. • November 2004-December 2006: Recipient of research fellow as Post-doc researcher at the Laboratory of Experimental Chemotherapy, Regina Elena National Cancer Institute, Rome. Supervisor Dr. Annamaria Biroccio • January 2004-October 2004: Fellow at the Proteomic Unit, Policlinico di Tor Vergata, Rome. Supervisor: Prof. Andrea Urbani. • October 2000-October 2003: PhD Fellow at the IBC-CNR, Monterotondo (RM). Supervisor: Dr. Stefano Alemà. • January 1998-October 2000: Attended as undergraduate student at the IBC-CNR, Monterotondo (RM). Supervisor: Dr. Stefano Alemà.
Grants · 2015-2019 My First Grant Airc · 2014-2015 FUV Post-doc fellowship · 2009-2011 FIRC fellowship · 2007-2008 CNRS Post-doc fellowship
Awards and Honors · Editorial board member of Journal of Experimental and Clinical Cancer Research.
|