Riccardo Vago RicercatoreMedicina

The group is focused on the study of the molecular and cellular mechanisms leading to the tumor onset and progression with the aim to develop personalized medicine approaches for unmet clinical needs through the identification of new targets and the comprehension of disease fundamentals and heterogeneity.

 

Main fields of research include, but are not limited to:

• Characterization of molecular and functional properties of evolving cancer. We have dissected the roles of long non-coding RNAs (lncRNAs) as drivers of oncogenic functions during carcinogenesis and tumor development. A special interest has been devoted to the lncRNA-mediated regulation of other non-coding elements eventually reverberating on protein effectors. Molecules involved in this axis have been considered as potential therapeutic targets and ad hoc intervention has developed to counteract their activity.
• Characterization and manipulation of extracellular vesicles to be exploited as drug delivery systems in cancer therapy. Being ascertained that extracellular vesicles play a key role in physiological as well as pathological processes, included cancer development and spreading, we have studied the transfer of cargoes promoting oncogenic modifications in recipient cells. We have developed different approaches to load vesicles with anti-tumor molecules and to equip them with targeting moieties to specifically hit cancer cells.
• Development of toxin-based therapeutics for targeted treatment of tumors. We have exploited the therapeutic potential of the plant toxin saporin, a potent poison able to kill intoxicated cells by inhibiting protein synthesis. We have explored the potential of a dual approach by developing saporin-based chimeric fusions with specific targeting or delivering toxin encoding DNA to the tumor site. We designed recombinant chimeric proteins able to selectively recognize features typical of cancer cells as well as tumor microenvironment. Direct activity and target specificity have been confirmed in vitro and currently translated into preclinical models.
• Identification of new diagnostic markers useful to implement non-invasive monitoring of tumor progression and treatment. Through collection of liquid biopsies form cancer patients (urines in urological malignancies), we have evaluated the presence of different molecules, such as lncRNAs, as key players in the tumor development, and have monitored their variations in the tumor progression. A panel of molecules has been defined to be employed as prognostic and predictive biomarker in the clinical setting.

• Study of the mechanisms leading to male infertility to identify factors involved in spermatozoa maturation and capacitation. By analyzing main components of the environment where spermatozoa have matured, we demonstrated that extracellular vesicles play a key role in the process of cell motility and capacitation. We have been investigating the role of the vesicle-carried molecules in such processes in normal conditions and in case of infertility.

Education:

2004                            Ph.D. degree in Genetic and Bio-molecular Sciences, University of Milano.

2000                            Single-cycle Master degree in Pharmaceutical Chemistry and Technology, University of Milano.

 

Professional experiences:

2015-present              Lecturer, “Biotechnological drugs and targeted delivery systems”, Appointed reference, University Vita-Salute San Raffaele, Milano, Italy

2014-present              Group leader, Urological Research Institute, Division of Experimental Oncology, IRCCS Ospedale San Raffaele, Milano, Italy

2013-2014                  Project leader, University of Milano-Bicocca, laboratory of Fermentations Chemistry and scientific consultant for the Department of Life Health and Environmental Sciences, University of L’Aquila

2011-present              Lecturer, “Biochemistry”, Appointed reference, University Vita-Salute San Raffaele, Milano, Italy

2007-2013                  Project leader, Human Molecular Genetics Unit (later Neurogenomics Unit), IRCCS Ospedale San Raffaele, Milano, Italy

2006-2007                  Post-doc, DNA Enzymology and Molecular Virology Unit, Institute of Molecular Genetics (IGM)-CNR, Pavia, Italy

2002 - 2004                PhD student, Protein Folding and Quality Control Laboratory, Institute for Research in Biomedicine (Bellinzona, Switzerland).

2001 - 2002                PhD student, Protein Transport and Secretion Unit, IRCCS Ospedale San Raffaele, Milano, Italy

2000 - 2001                Research fellow, Biotechnology Unit, IRCCS Ospedale San Raffaele, Milano, Italy

2000                           Visiting fellow, Leukemia Research Laboratory (Southampton General Hospital, UK)

Gori A, Romanato A, Greta B, Strada A, Gagni P, Frigerio R, Brambilla D, Vago R, Galbiati S, Picciolini S, Bedoni M, Daaboul G, Chiari M, Cretich M (2020) “Membrane-binding peptides for extracellular vesicles on-chip analysis” J Extracell Vesicles. 9:1

Vago R. Ravelli A, Bettiga A, Casati S, Lavorgna G, Benigni F, Salonia A, Montorsi F, Orioli M, Ciuffreda P, Ottria R. (2020) “Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage” Cancers. 12(4), 870

Giacomini E, Makieva S, Murdica V, Vago R, Viganó P. (2020) “Extracellular Vesicles as a Potential Diagnostic Tool in Assisted Reproduction“ Curr Opin Obstet Gynecol. Mar 19

Zuppone S, Assalini C, Minici C, Bertagnoli S, Branduardi P, Degano M, Fabbrini MS, Montorsi F, Salonia A, Vago R. (2020) “The anti-tumoral potential of the saporin-based uPAR-targeting chimera ATF-SAP” Sci. Rep. 13;10(1):2521.

Murdica V, Cermisoni G, Zarovni N, Salonia A, Viganò P, Vago R (2019) “Proteomic analysis reveals the negative modulator of sperm function glycodelin over-represented in semen isolated from asthenozoospermic patients” Hum.Rep.; 1;34(8):1416-1427

Zuppone S, Fabbrini MS, Vago R (2019) “Hosts for Hostile Protein Production: The Challenge of Recombinant Immunotoxin Expression” Biomedicines. 17;7(2)

Murdica, V, Giacomini E, Alteri A, Bartolacci A, Cermisoni G, Zarovni N, Papaleo E, Montorsi F, Salonia A, Viganò P, Vago R (2019) “Seminal plasma of men with severe asthenozoospermia contain exosomes affecting spermatozoa motility and capacitation“ Fertil Steril. ;111(5):897-908.e2

Vago R, Salonia A. (2019) “Re: Circulating Extracellular Vesicles in Human Disease” Eur Urol. 75(2):342-343

Fabbrini MS, Katayama M, Nakase I, Vago R (2017) “Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)” Toxins 2;9(10)

Giacomini E, Vago R, Sanchez AM, Podini P, Zarovni N, Murdica V, Rizzo R, Bortolotti D, Candiani M, Viganò P. (2017) “Secretome of in vitro cultured human embryos contains extracellular vesicles that are uptaken by the maternal side” Sci. Rep. 12;7(1):5210

Vago R, Bettiga A, Salonia A, Ciuffreda P, Ottria R. (2017) “Development of new inhibitors for N-acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer” Bioorg Med Chem. 1;25(3):1242-1249

Errico Provenzano A, Posteri R, Giansanti F, Angelucci F, Flavell SU, Flavell DJ, Fabbrini MS, Porro D, Ippoliti R, Ceriotti A, Branduardi P, Vago R. (2016) “Optimization of construct design and fermentation strategy for the production of bioactive ATF-SAP, a saporin based anti-tumoral uPAR-targeted chimera”. Microb Cell Fact. 14;15(1):194

Vago R, Collico V, Zuppone S, Prosperi D, Colombo M. (2016) “Nanoparticle-mediated delivery of suicide genes in cancer therapy”. Pharmacol Res. 111:619-41

Kooijmans SA, Schiffelers RM, Zarovni N, Vago R. (2016) “Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: new nanotools for cancer treatment”. Pharmacol Res. 111:487-500

Lavorgna G, Vago R, Sarmini M, Montorsi F, Salonia A, Bellone M. (2016) “Long non-coding RNAs as novel therapeutic targets in cancer” Pharmacol Res. 110:131-8

Della Cristina P, Castagna M, Lombardi A, Barison E, Tagliabue G, Ceriotti A, Koutris I, Di Leandro L, Giansanti F, Vago R, Ippoliti R, Flavell SU, Flavell DJ, Colombatti M, Fabbrini MS. (2015) “Systematic comparison of single-chain Fv antibody-fusion toxin constructs containing Pseudomonas Exotoxin A or saporin produced in different microbial expression systems” Microb Cell Fact. 13;14(1):19.

Daniele T, Hurbain I, Vago R, Casari G, Raposo G, Tacchetti C, Schiaffino MV. (2014) “Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis” Curr Biol. 17;24(4):393-403

De Fusco M, Vago R, Striano P, Di Bonaventura C, Zara F, Mei D, Kim MS, Muallem S, Chen Y, Wang Q, Guerrini R, Casari G (2014) “The α2B adrenergic receptor is mutant in cortical myoclonus and epilepsy” Annals of Neurology 75(1):77-87

Michiorri S, Gelmetti V, Giarda E, Lombardi F, Romano F, Marongiu R, Nerini-Molteni S, Sale P, Vago R, Arena G, Torosantucci L, Cassina L, Russo MA, Dallapiccola B, Valente EM, Casari G. (2010) “The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy” Cell Death Differ. 2010 Jun;17(6):962-74.

Vago R, Leva V, Biamonti G, Montecucco A. (2009) “DNA ligase I and Nbs1 proteins associate in a complex and colocalize at replication factories” Cell Cycle. 15;8(16):2600-7.

Soza S, Leva V, Vago R, Ferrari G, Mazzini G, Biamonti G, Montecucco A. (2009) “DNA ligase I deficiency leads to replication-dependent DNA damage and impacts cell morphology without blocking cell cycle progression” Mol Cell Biol. 29(8):2032-41.

Zarovni N*, Vago R*, Soldà T, Monaco L, Fabbrini M.S. (2007) “Saporin as a novel suicide gene in cancer gene therapy” Cancer Gene Ther. 14(2):165-73.

Vago R., Marsden C.J., Lord J.M., Ippoliti R., Flavell D.J., Flavell S.U., Ceriotti A. and Fabbrini M.S. (2005). “Saporin and ricin, two ribosome-inactivating proteins from plants, differ in their routes of entry into mammalian cells” FEBS J. 272(19):4983-95

Eriksson, K. K.; Vago, R.; Calanca, V.; Galli, C.; Paganetti, P.; Molinari, M. (2004). "EDEM contributes to maintenance of protein folding efficiency and secretory capacity." J Biol Chem 279(43): 44600-5.