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| First Name: | Massimo | | Last Name: | Stefani | | Title: | Professor | | Advanced Degrees: | Biology | | Affiliation: | University of Florence | | Department: | Dept. Biochemnical Sciences | | Street Address 1: | Viale Morgagni 50 | | City: | Florence | | Zip/Postal Code: | 50134 | Country/Territory: | Italy | | Phone: | +39.0554598 | | Fax: | +39.0554598905 | | Email Address: |  |
Disclosure:
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Member reports no financial or other potential conflicts of interest. [Last Modified: 27 April 2005]
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View all comments by Massimo Stefani
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Molecular and Cell biology, Apoptosis/Cell cycle, Oxidative Stress, Protein structure/chemistry
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Massimo Stefani was born in Pisa, on 31/7/1950 and graduated in Biological Sciences at the University of Firenze. Since then he continued to work at the Institute of Biochemistry. From 1/11/1975 through 31/7/1981 he got a fellowship from the University of Florence. Since 1/8/1981 he was researcher at the Department of Biochemistry of the University of Florence. In 1990 he won a competition for Full professor of Biochemistry at the University of Siena. Since 1993 he is full professor of Biochemistry at the Department of Biochemical Sciences of the University of Florence.
His scientific interests have been focused on the study of the structure funcion relatioship of phosphomonohydrolases, particularly acylphosphatases and phosphotyrosine protein phosphatases. More recently, he has dedicated his efforts to the study of molecular biology issues such as protein folding, misfolding and aggregation of model proteins such as acylphosphatase, beta2 microglobulin and HypF and the molecular mechanisms underlying amyloid aggregation and aggregate cytotoxicity on living systems. The results of his researches have been reported in over 80 scientific papers published in outstanding international journals.
He has collaborated, and presently collaborates with many foreign and italian researchers, notably Prof. C.M. Dobson, University of Cambridge, Dr. R. Melki, CNRS, Paris, Prof. P. Nordlund, University of Stockholm, Prof. V. Bellotti, University of Pavia, Prof. P. Pucci and Prof. M. Rossi, University of Napoli, Prof. M. Bolognesi and Prof. A. Gliozzi, University of Genova, Prof. P. Viglino, University of Udine. He has been, and presently is responsible of research projects granted by CNR and MIUR (PRIN and FIIRB) as well as partner in projects CNR, UE and MURST PRIN. He is member of the “Center of Excellence for “Molecular and Clinical Studies on chronic, inflammatory, degenerative and tumoural diseases for the development of new therapies” of the University of Florence.
He has participated to several international congresses and meetings as invited speaker, has organized the international meeting HFSP/EU “Protein Phosphatases” and has been Co-organizer and member of the Scientific Committee of the V European Symposium of the Protein Society. He has organized the laboratory of chemical synthesis of peptides at the Department of Biochemistry of the University of Firenze. He is member of the Società Italiana di Biochimica e Biologia Molecolare and of the Protein Society; he is Executive Editor of the Italian Journal of Biochemistry.
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• The crystal structure of a low molecular weight phosphotyrosine protein phosphatase (X.D. Su, N. Taddei, M. Stefani, G. Ramponi, and P. Nordlund) Nature (1994) 6490: 575-578.
• Mutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding (F. Chiti, N. Taddei, P.M. White, M. Bucciantini, F. Magherini, M. Stefani e C.M. Dobson) Nat. Struct. Biol. (1999) 6:1005-1009.
• Designing conditions for in vitro formation of amyloid protofilaments and fibrils (F. Chiti, P. Webster, N. Taddei, A. Clark, M. Stefani, G. Ramponi e C.M. Dobson) Proc. Natl. Acad. Sci. USA (1999) 96:3590-94.
• Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases (M. Bucciantini, E. Giannoni, F. Chiti, F. Baroni, L. Formigli, J. Zurdo, N. Taddei, G. Ramponi, C.M. Dobson & M. Stefani) Nature (2002) 416: 507-511.
• Comparison of the folding processes of distantly related proteins. Importance of hydrophobic content in folding (G. Calloni, N. Taddei, K.W. Plaxco, G. Ramponi, M. Stefani & F. Chiti) J Mol. Biol. (2003) 330: 577-91.
• Rationalization of the effects of mutations on peptide and protein aggregation rates (F. Chiti, M. Stefani, N. Taddei, G. Ramponi & C.M. Dobson) Nature (2003) 424: 805-808.
• Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution (M. Stefani & C.M. Dobson). J. Mol. Med. (2003) 81: 678-699.
• Monitoring the process of HypF fibrillization and liposome permeabilization by protofibrils (Relini, A., Torrassa, S., Rolandi, R., Gliozzi, A., Rosano, C., Canale, C., Bolognesi, M., Plakoputsi, G., Bucciantini, M., Chiti, F. & Stefani, M.) J. Mol. Biol. (2004) 338:943-957.
• Pre-fibrillar amyloid protein aggregates share common features of cytotoxicity. (Bucciantini M, Calloni G, Chiti F, Formigli L, Nosi D, Dobson CM, Stefani M) J Biol Chem. (2004) 279:31374-31382.
• Patterns of cell death triggered in two different cell lines by HypF-N pre-fibrillar aggregates (M. Bucciantini, S. Rigacci, A. Berti, L. Pieri, C. Cecchi, D. Nosi, L. Formigli, F. Chiti & M. Stefani) FASEB J. (2005) 19:437-439.
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The interaction of protein/peptides with biological surfaces particularly but not exclusively membranes) has not yet been adequately investigated; in particular, I consider particularly intriguing and of fundamental importance to better address the relation between physicochemical properties of biological surfaces, membrane lpid composition, protein/peptide interaction with membranes, the effect of the latter in increasing peptide/protein local concentration thus favouring oligomerization and permeabilization by the aggregates. |
Kayed et al. Science 300, 486.489 (2003)
Demuro et al. J.B.C. 2005 in press
Kayed et al. J.B.C. 279, 46363-6 (2004) |
A microarray and proteomic approach to investigate the patterns of gene expression in differing cell types engineered to express aggregation disease-related proteins such as Abeta peptides and alpha-synuclein mutants. |
I believe that, at least in most cases (with possible exceptions), amyloid toxicity proceeds from misfolded monomers/oligomers whose structural instability, associated with exposure of hydrophobic patches following partial unfolding, leads them to interact easily with cell components, notably membranes or other surfaces. Membrane interaction is followed by perturbation of membrane integrity with modifications of membrane permeability and, possibly of specific membrane functions such as ion transport and signalling. The derangement of ion homeostasis and the increase of free calcium ions (and possibly of other ions) activate cell metabolism to sustain the increased ion pump activities to clear the excess ions. The consequent ROS increase may subsequently impair ion pumps and allow more calcium ions to enter the cell and be trapped mostly into mitochondria, resulting in impairment of such organelles and release of apoptotic stimuli tergeting the cell to death. |
An intriguing approach to further support this view could be investigating whether cell types with differing susceptibilities to impairment by the toxic aggregates are endowed with significantly more efficient basal biochemical tools helping them to better counteract free calcium ingress and the subsequent oxidative stress. |
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