Palma Mangione
Palma Mangione
affiliation: Università di Pavia
research area(s): Chemical Biology
Course: Biomolecular Sciences and Biotechnology
University/Istitution: Istituto Universitario di Studi Superiori, Pavia
Assistant Professor of Biochemistry, University of Pavia

• 1994 University of Pavia (Italy), Pharmaceutical Chemistry and Technology Degree
• 1995-1998 University of Pavia, PhD of Biochemistry
• 2005-2007 Visiting Senior Research Fellow, Centre for Amyloidosis and Acute Phase Proteins, Royal Free and University College Medical School, London, U.K.
The common theme to Dr Mangione's research projects has been the characterization of the structural bases of human globular protein pathological conversion into amyloid fibrils. This research activity comprises all the basic biochemical techniques, production of recombinant proteins and their chemical characterization. A wide range of spectroscopic techniques performed either at equilibrium or under dynamic conditions are also required to elucidate structural, kinetic and thermodynamic aspects related to the fibrillogenesis of amyloidogenic human proteins with particular regard to lysozyme, beta 2-microglobulin and apolipoprotein A-I. In collaboration with Prof Pepys group (Center for Amyloidosis and acute phase proteins, UCL, London, UK) Dr Mangione is involved in a drug discovery project aimed at the identification of new drugs for treatment and prevention of acquired and hereditary human systemic transthyretin amyloidosis.
• Giorgetti S., Raimondi S., Pagano K., Relini A., Bucciantini M., Corazza A., Fogolari F., Codutti L., Salmona M., Mangione P., Colombo L., De Luigi A., Porcari R., Gliozzi A., Stefani M., Esposito G., Bellotti V., Stoppini M. (2011) Effect of tetracyclines on the dynamics of formation and destructuration of {beta}2-microglobulin amyloid fibrils. J Biol Chem; 286:2121-31
• Marchesi M., Parolini C., Valetti C., Mangione P., Obici L., Giorgetti S., Raimondi S., Donadei S., Gregorini G., Merlini G., Stoppini M., Chiesa G., Bellotti V. (2011) The intracellular quality control system down-regulates the secretion of amyloidogenic apolipoprotein A-I variants: A possible impact on the natural history of the disease. Biochim Biophys Acta; 1812:87-93
• Bodin K., Ellmerich S., Kahan M.C., Tennent G.A., Loesch A., Gilbertson J.A., Hutchinson W.L., Mangione P.P., Gallimore J.R., Millar D.J., Minogue S., Dhillon A.P., Taylor G.W., Bradwell A.R., Petrie A., Gillmore J.D., Bellotti V., Botto M., Hawkins P.N., Pepys M.B. (2010) Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature; 468:93-97
• Kolstoe S.E., Mangione P.P., Bellotti V., Taylor G.W., Tennent G.A., Deroo S., Morrison A.J., Cobb A.J., Coyne A., McCammon M.G., Warner T.D., Mitchell J., Gill R., Smith M.D., Ley S.V., Robinson C.V., Wood S.P., Pepys M.B. (2010) Trapping of palindromic ligands within native transthyretin prevents amyloid formation. Proc Natl Acad Sci U S A; 107:20483-8
Project Title:
Characterization of new ligands for human transthyretin
Aim of the project is the characterization of new compounds for prophylaxis and treatment of senile and hereditary transthyretin (TTR) amyloidosis, fatal adult onset diseases caused by tissue deposition of amyloid fibrils composed respectively of wild type and variant plus wild type TTR. For amyloidogenesis to occur, the TTR tetramer must dissociate into four folded monomers and undergo partial denaturation in order to subsequently misassemble into a spectrum of aggregate structures including cross-β-sheet amyloid fibrils. Therefore to reduce abundance of the fibril precursor, which is the only effective treatment of any form of systemic amyloidosis, we aim at either prevention of TTR misfolding or depletion of the protein. Novel ligands will be investigated to characterize: (i) binding of the novel constructs in vitro; (ii) TTR stabilization in vitro; (iii) efficacy in vivo by using suitable models.