Extracellular vesicles (EVs) are lipid-composed particles, in the range of nanometers, secreted from the cells. EVs entrap several molecules, such as different kind of lipids, RNA, proteins, and metabolites that can be produced to influence recipient cells, therefore mediating a sort of communication. Cells from different tissues release billions of circulating EVs that can be retrieved from liquid biopsies.
We study EVs with three major goals:
- Exploit them to develop novel precision medicine tools: We sought to apply high-throughput procedures to isolate EVs from cell culture media or biological fluids (blood, urine, CSF, saliva) and develop quantitative approaches to probe markers mirroring the cell heterogeneity that characterizes complex disorders;
- Apply quantitative technologies to understand the functional effect of the horizontal material transfer to recipient cells: Mostly focused at RNA and protein levels and on the discovery of modulators of their sorting into EVs;
- Build novel ex-vivo therapeutic particles: EVs expose specific transmembrane proteins found in the cells that have originated them. Several tools for EV engineering and production can be explored for the design of a new generation of vectors with a defined bio-distribution and promising anti-cancer effects.
- Vito Giuseppe D'Agostino, PI
- Jessica Corsi, pre-doc fellowship
- Chiara Tessaro, Bachelor student
- Elena Elez, VHIO, Spain
- Stefan Lehr, DDZ, Germany
- Tero Aittokallio, FIMM, Finland
- Robin Ristl, MUW, Austria
Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, Lunelli C, Pederzolli C, Pavan P, la Marca G, Pasini L, Ulivi P, Beltran H, Demichelis F, Provenzani A, Quattrone A, D'Agostino VG. Ultrasensitive detection of cancer biomarkers by nickel-based isolation ofpolydisperse extracellular vesicles from blood. https://doi.org/10.1016/j.ebiom.2019.04.039
D'Agostino VG, Sighel D, Zucal C, Bonomo I, Micaelli M, Lolli G, Provenzani A, Quattrone A, Adami V. Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery. SLAS Discov. 2019 Mar;24(3):314-331. doi: 10.1177/2472555218818065.
Tebaldi T, Zuccotti P, Peroni D, Köhn M, Gasperini L, Potrich V, Bonazza V, Dudnakova T, Rossi A, Sanguinetti G, Conti L, Macchi P, D'Agostino V, Viero G, Tollervey D, Hüttelmaier S, Quattrone A. HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA. Mol Cell. 2018 Jul 19;71(2):256-270.e10. doi: 10.1016/j.molcel.2018.06.032.
D'Agostino VG, Lal P, Mantelli B, Tiedje C, Zucal C, Thongon N, Gaestel M, Latorre E, Marinelli L, Seneci P, Amadio M, Provenzani A. Dihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function. Sci Rep. 2015 Nov 10;5:16478. doi: 10.1038/srep16478.
D'Agostino VG, Minoprio A, Torreri P, Marinoni I, Bossa C, Petrucci TC, Albertini AM, Ranzani GN, Bignami M, Mazzei F. Functional analysis of MUTYH mutated proteins associated with familial adenomatous polyposis. DNA Repair (Amst). 2010 Jun 4;9(6):700-7. doi: 10.1016/j.dnarep.2010.03.008.