Extracellular vesicles and toxins
The Extracellular vesicles and toxins 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 identification of new targets and understanding 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 dissect the roles of lncRNAs as drivers of oncogenic functions during carcinogenesis and tumor development by regulating other non-coding elements and protein effectors.
- Development of toxin-based therapeutics for targeted treatment of tumors. We designed recombinant chimeric proteins as fusions between the plant toxin saporin and the peptides able to selectively recognize features typical of cancer cells and tumor microenvironment. Direct activity and target specificity are confirmed in vitro and translated into preclinical models.
- Development of exosomes as drug delivery systems in cancer therapy. We have developed different approaches to load vesicles with anti-tumor molecules and equip them with targeting moieties to specifically hit tumor cells.
- Identification of biomarkers to implement non-invasive monitoring of tumor progression. Through collection of liquid biopsies from cancer patients (urines in urological malignancies), we evaluate the expression of lncRNAs, as key players in the tumor development, and investigate their employment as prognostic and predictive biomarkers in the clinical setting.
- Study of the mechanisms leading to male infertility to identify defective spermatozoa and enhance fertilization success rate. By analyzing main components of the environment where spermatozoa have matured, we demonstrated that exosomes play a key role in the process of cell motility and capacitation and can distinguish healthy, fertilizing spermatozoa from defective, non-fertilizing ones.
Vago R. Ravelli A, Bettiga A, Casati S, Lavorgna G, Benigni F, Salonia A, Montorsi F, Orioli M, Ciuffreda P, Ottria R. “Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage”, Cancers, 2020, 12(4), 870.
Zuppone S, Assalini C, Minici C, Bertagnoli S, Branduardi P, Degano M, Fabbrini MS, Montorsi F, Salonia A, Vago R. “The anti-tumoral potential of the saporin-based uPAR-targeting chimera ATF-SAP” Sci. Rep. 2020, 13;10(1):2521.
Murdica V, Cermisoni G, Zarovni N, Salonia A, Viganò P, Vago R, “Proteomic analysis reveals the negative modulator of sperm function glycodelin over-represented in semen isolated from asthenozoospermic patients” Hum.Rep.; 2019, 1;34(8):1416-1427
Zuppone S, Fabbrini MS, Vago R, “Hosts for Hostile Protein Production: The Challenge of Recombinant Immunotoxin Expression” Biomedicines. 2019, 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 “Seminal plasma of men with severe asthenozoospermia contain exosomes affecting spermatozoa motility and capacitation“ Fertil Steril. 2019, 111(5):897-908.
Vago R, Salonia A. “Re: Circulating Extracellular Vesicles in Human Disease” Eur Urol. 2019, 75(2):342- 343
Fabbrini MS, Katayama M, Nakase I, Vago R “Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)” Toxins, 2017, 2;9(10)
Giacomini E, Vago R, Sanchez AM, Podini P, Zarovni N, Murdica V, Rizzo R, Bortolotti D, Candiani M, Viganò P. “Secretome of in vitro cultured human embryos contains extracellular vesicles that are uptaken by the maternal side” Sci. Rep. 2017, 12;7(1):5210
Vago R, Bettiga A, Salonia A, Ciuffreda P, Ottria R. “Development of new inhibitors for N- acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer” Bioorg Med Chem. 2017, 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. “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. 2016, 14;15(1):194
Vago R, Collico V, Zuppone S, Prosperi D, Colombo M. “Nanoparticle-mediated delivery of suicide genes in cancer therapy”. Pharmacol Res. 2016, 111:619-41
Kooijmans SA, Schiffelers RM, Zarovni N, Vago R. “Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: new nanotools for cancer treatment”. Pharmacol Res. 2016,111:487-500
Lavorgna G, Vago R, Sarmini M, Montorsi F, Salonia A, Bellone M. “Long non-coding RNAs as novel therapeutic targets in cancer” Pharmacol Res. 2016, 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. “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. 2015, 13;14(1):19.
Daniele T, Hurbain I, Vago R, Casari G, Raposo G, Tacchetti C, Schiaffino MV. “Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis” Curr Biol. 2014, 17;24(4):393-403