Maria Francesca Mossuto

Research Interests

Immunoglobulins, besides being the principal players of physiological immune response, play an important role in many pathologies such as Plasma cell dyscrasias, and in biotechnological processes and pharmaceutical industry.

Due to many years of experience in the amyloid field, the focus of my research is on Immunoglobulin (Ig) misfolding and aggregation, a process often reported in Multiple Myeloma patients. To study this process I take advantage of a multidisciplinary approach based on

- biophysics (structure of Ig aggregates);

- molecular biology (development of fluorescent Ig to follow Ig trafficking, aggregation and clearance in vivo);

- cellular biology (to study how different cell types react to the formation and the presence of Ig aggregates).

The final aim is to obtain a clear scenario of Ig misfolding and aggregation in cells to identify new therapeutic targets to use against plasma cell diseases such as Multiple Myeloma.

Publications

S. Vavassori, M. Cortini, S. Masui, S. Sannino, T. Anelli, I.R. Caserta, C. Fagioli, M.F. Mossuto, A. Fornili, E. van Anken, M. Degano, K. Inaba, R. Sitia. A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly. Mol Cell. In press

M.F. Mossuto, B. Bolognesi, B. Guixer, A. Dhulesia, F. Agostini, J.R. Kumita, G.G. Tartaglia, M. Doumulin, C.M. Dobson, X. Salvatella. (2011) Disulfide bonds reduce the toxicity of the amyloid fibrils formed by an extracellular protein. Angewandte Chemie-International Edition 50, 7048-7051.

A. Baldwin, T. Knowles, G. Tartaglia, A. Fitzpatrick, G. Devlin, S. Shammas, C. Waudby, M.F. Mossuto, S. Gras, J. Christodoulou, S. Anthony-Cahill, P. Barker, M. Vendruscolo, C.M. Dobson (2011) Metastability of Native Proteins and the Phenomenon of Amyloid Formation. J Am Chem Soc 133, 14160-14163.

A.K. Buell, A. Dhulesia, M.F. Mossuto, N. Cremades, J.R. Kumita, M. Dumoulin, M.E. Welland, T.P.J. Knowles, X. Salvatella, C.M. Dobson. (2011) Population of non-native states of lysozyme mutants drives amyloid fibrils formation. J Am Chem Soc 133, 7737-7743.

A. Dhulesia, N. Cremades, J.R. Kumita, S.D. Hsu, M.F. Mossuto, M. Dumoulin, D. Nietlispach, M. Akke, X. Salvatella, C.M. Dobson. Local cooperativity in the amyloidogenic state of human lysozyme observed at atomic resolution. J Am Chem Soc 132, 15580-15588.

M.F. Mossuto, A. Dhulesia, G. Devlin, E. Frare, J.R. Kumita, P. Polverino de Laureto, M. Dumoulin, A. Fontana, X. Salvatella, C.M. Dobson. (2010) The non-core regions of lysozyme amyloid fibrils give rise to cytotoxicity. J. Mol. Biol. 402, 783-796.

M.F. Mossuto, E. Frare, P. Polverino de Laureto, S. Tolin, L. Menzer, M. Dumoulin, C.M. Dobson, A. Fontana. (2009) Characterization of oligomeric species on the aggregation pathway of human lysozyme. J. Mol. Biol. 387, 17-27.

S. Campioni, M.F. Mossuto, S. Torrassa. G. Calloni. A. Relini, P. Polverino de Laureto, A. Fontana and F. Chiti. (2007) Conformational properties of the aggregation precursor state of HypF-N. J. Mol. Biol. 379, 554-567.

E. Frare, M.F. Mossuto, P. Polverino de Laureto, M. Dumoulin, C.M. Dobson and A. Fontana. (2006). Identification of the Core Structure of Lysozyme Amyloid Fibrils by Proteolysis. J. Mol. Biol. 361, 551-561.

P. Polverino de Laureto, E. Frare, F. Battaglia, M.F. Mossuto, V. Uversky and A. Fontana. (2005). Protein dissection enhances the amyloidogenic properties of alpha-lactalbumin. FEBS Journal. 272, 2176-2188.