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Protein biochemistry and protein misfolding diseases
Bellotti lab

Vittorio Bellotti, PI


Phone: (+39) 0382 987189

Web site:

Lab members

Vittorio Bellotti, PI, Full Professor

Palma Patrizia Mangione,  Associate Professor 

Sofia Giorgetti, Associate Professor 

Sara Raimondi, Reseracher 

Francesca Lavatelli, Reseracher 

Loredana Marchese, Post-Doc 

Maria Chiara Mimmi, Post-Doc 

Gugliemo Verona, Lecturer 

Diana Canetti,Post-Doc 

Valentina Mondani, PhD Student 

Paola Nocerino, PhD Student 

Alma Baruffaldi, Research fellow 

Systemic amyloidoses are a group of severe diseases, in which human proteins lose their native globular structure and aggregate as extracellular amyloid fibrils, thus damaging the architecture and function of affected organs. Many forms of systemic amyloidoses are aging-related, and this problem is progressively growing in parallel to the increased life expectancy of our society. The mechanisms that govern the onset, anatomical distribution and progression of amyloid deposition are still poorly understood.
Our research aims to elucidate the mechanism of conversion of amyloidogenic globular proteins to fibrils, in the perspective of understanding the events occurring in the physiological environment in the major forms of systemic amyloidosis. To this aim, we exploit biocompatible in vitro and in vivo experimental systems, and we explore the biological factors that modulate the natural history of the disease, mainly the interaction with components of the microenvironment, biomechanical forces, post-translational modifications.
The current research activity of the laboratory is focused on:
- Transthyretin (TTR), causing hereditary (ATTRh) or aging-related (ATTRwt) ATTR amyloidosis;
- β2-microglobulin (β2-m), causing hereditary or dialysis-associated amyloidosis;
- Immunoglobulin light chains, causing light chain amyloidosis (AL amyloidosis).
Our research is based on advanced technologies, including NMR, spectroscopic and proteomics approaches. Specifically developed experimental systems include decellularized tissues and animal models, in particular transgenic C. elegans strains expressing β2-m isoforms, and a murine model for a pathogenic TTR variant. Through these systems we can test, at a preclinical level, potential therapeutic strategies under developme

Slamova I, Adib R, Ellmerich S, Golos M, Gilbertson J, Botcher N, Canetti D, Taylor GW, Rendell NB, Tennent GA, Verona G, Porcari R, Mangione PP, Gillmore JD, Pepys MB, Bellotti V, Hawkins PN, Al-Shawi R, Simons JP. Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis. Nature Commun 2021; 7:7112

Raimondi S, Mangione PP, Verona G, Canetti D, Nocerino P, Marchese L, Piccarducci R, Mondani V, Faravelli G, Taylor GW, Gillmore JD, Corazza A, Pepys MB, Giorgetti S, Bellotti V. Comparative study of the stabilities of synthetic in vitro and natural ex vivo transthyretin amyloid fibrils. J Biol Chem 2020; 295:11379-11387

Lavatelli F, Mazzini G, Ricagno S, Iavarone F, Rognoni P, Milani P, Nuvolone M, Swuec P, Caminito S, Tasaki M, Chaves-Sanjuan A, Urbani A, Merlini G, Palladini G. Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis. J Biol Chem. 2020;295:16572-16584

Marcoux J, Mangione PP, Porcari R, Degiacomi MT, Verona G, Taylor GW, Giorgetti S, Raimondi S, Sanglier-Cianférani S, Benesch JL, Cecconi C, Naqvi MM, Gillmore JD, Hawkins PN, Stoppini M, Robinson CV, Pepys MB, Bellotti V. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. EMBO Mol Med. 2015;7:1337-49

Valleix S, Gillmore JD, Bridoux F, Mangione PP, Dogan A, Nedelec B, Boimard M, Touchard G, Goujon JM, Lacombe C, Lozeron P, Adams D, Lacroix C, Maisonobe T, Planté-Bordeneuve V, Vrana JA, Theis JD, Giorgetti S, Porcari R, Ricagno S, Bolognesi M, Stoppini M, Delpech M, Pepys MB, Hawkins PN, Bellotti V. Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin. N Engl J Med. 2012;366:2276-83