Overview
Extracellular vesicles (EVs) are heterogeneous lipid-composed particles massively secreted from the cells. EVs are constituted by different kind of lipids, RNA, proteins, and metabolites cargoes that can be exchanged by neighbouring or distant cells through body fluids. Circulating EVs can be exploited in liquid biopsies or manipulated to design new vehicles for horizontal transfer of biological material.
Research directions
We study EVs with three major goals:
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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 vehicles
EVs expose specific transmembrane proteins that can be exploited to potentially direct their biodistribution. Several tools can be explored for generating EV sub-populations characterized by a defined biodistribution and/or anti-cancer effects.
Group members
- Vito Giuseppe D’Agostino, PI
- Michela Notarangelo, Postdoc
- Elena Gurrieri, PhD Student
- Fabrizio Fabbiano, PhD Student
- Jessica Corsi, PhD Student
- LM and LT Students
Collaborations
- Elena Elez, VHIO, Spain
- Stefan Lehr, DDZ, Germany
- Tero Aittokallio, FIMM, Finland
- Robin Ristl, MUW, Austria
Selected publications
Pasetto L, Callegaro S, Corbelli A, Fiordaliso F, Ferrara D, Brunelli L, Sestito G, Pastorelli R, Bianchi E, Cretich M, Chiari M, Potrich C, Moglia C, Corbo M, Sorarù G, Lunetta C, Calvo A, Chiò A, Mora G, Pennuto M, Quattrone A, Rinaldi F, D'Agostino VG, Basso M, Bonetto V. Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis. Mol Neurodegener. 2021 Aug 10;16(1):52. doi: 10.1186/s13024-021-00470-3. PMID: 34376243; PMCID: PMC8353748.
Pasini L, Notarangelo M, Vagheggini A, Burgio MA, Crinò L, Chiadini E, Prochowski AI, Delmonte A, Ulivi P, D'Agostino VG. Unveiling mutational dynamics in non-small cell lung cancer patients by quantitative EGFR profiling in vesicular RNA. Mol Oncol. 2021 Sep;15(9):2423-2438. doi: 10.1002/1878-0261.12976. Epub 2021 May 20. PMID: 33942501; PMCID: PMC8410558.
Mangiapane G, Parolini I, Conte K, Malfatti MC, Corsi J, Sanchez M, Pietrantoni A, D'Agostino VG, Tell G. Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes. J Biol Chem. 2021 Jan-Jun;296:100569. doi: 10.1016/j.jbc.2021.100569. Epub 2021 Mar 19. PMID: 33753167; PMCID: PMC8080531.
Notarangelo M, Ferrara D, Potrich C, Lunelli L, Vanzetti L, Provenzani A, Basso M, Quattrone A, D'Agostino VG. Rapid Nickel-based Isolation of Extracellular Vesicles from Different Biological Fluids. Bio Protoc. 2020 Feb 5;10(3):e3512. doi: 10.21769/BioProtoc.3512. PMID: 33654737; PMCID: PMC7842538.
Fabbiano F, Corsi J, Gurrieri E, Trevisan C, Notarangelo M, D'Agostino VG. RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins? J Extracell Vesicles. 2020 Dec;10(2):e12043. doi: 10.1002/jev2.12043. Epub 2020 Dec 28. PMID: 33391635; PMCID: PMC7769857.
Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, Lunelli L, 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 of polydisperse extracellular vesicles from blood. EBioMedicine. 2019 May;43:114-126. doi: 10.1016/j.ebiom.2019.04.039. Epub 2019 Apr 29. PMID: 31047861; PMCID: PMC6558028.
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. Epub 2019 Jan 7. PMID: 30616427.
Dalle Vedove A, Spiliotopoulos D, D'Agostino VG, Marchand JR, Unzue A, Nevado C, Lolli G, Caflisch A. Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains. ChemMedChem. 2018 Jul 18;13(14):1479-1487. doi: 10.1002/cmdc.201800234. Epub 2018 Jun 21. PMID: 29770599.
Lal P, Cerofolini L, D'Agostino VG, Zucal C, Fuccio C, Bonomo I, Dassi E, Giuntini S, Di Maio D, Vishwakarma V, Preet R, Williams SN, Fairlamb MS, Munk R, Lehrmann E, Abdelmohsen K, Elezgarai SR, Luchinat C, Novellino E, Quattrone A, Biasini E, Manzoni L, Gorospe M, Dixon DA, Seneci P, Marinelli L, Fragai M, Provenzani A. Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic Acids Res. 2017 Sep 19;45(16):9514-9527. doi: 10.1093/nar/gkx623. PMID: 28934484; PMCID: PMC5766160.
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 posttranscriptional function. Sci Rep. 2015 Nov 10;5:16478. doi: 10.1038/srep16478. PMID: 26553968; PMCID: PMC4639722.