- Vivi Padova
- Il Bo
1988 Degree in Biological Sciences "summa cum laude", University of Padova.
1994 PhD in Molecular and Cellular Biology and Pathology, University of Padova.
2014 National academic qualification as Associate professor of Molecular Biology (BIO/11)
01.11.1993/31.10.1994: Telethon fellowship “Molecular analysis of mitochondrial cytopathology with deficit of cytochrome c oxidase.”
01.11.1994/31.05.9: Technical collaborator at the “Istituto Policattedra della Facoltà di Biotecnologie Agro Industriali”, University of Verona.
01/06/1998/30.09.2001 Technical collaborator at the “Department of Biomedical and Experimental Sciences”, University of Padova.
01.10.2001 to date Assistant Professor, grouping discipline Molecular Biology (BIO/11), Department of Biomedical Sciences, School of Medicine, University of Padova.
2002-2012: course of Molecular Biology, Laurea Triennale Interfacoltà in Biotecnologie Sanitarie, University of Padova
2010-2011, 2011-2012: course of Molecular Biology, Laurea Magistrale in Farmacia, University of Padova
2008-to date: course of Molecular Biology II, Laurea Magistrale in Biotecnologie Farmaceutiche, University of Padova
By the end of the 90’s, Dorianna Sandonà started to investigate the role of sarcoglycan (SG) complex in the patho-physiology of skeletal muscles. She studied the physiology of SG-complex assembly and trafficking and the pathological consequences of single point mutations of α-sarcoglycan responsible for a rare genetic disorder called type-2D Limb Girdle Muscular Dystrophy (LGMD2D). She established that sarcoglycans undergo folding, maturation and complex assembly in the Endoplasmic Reticulum (ER) before being delivered to the plasma membrane. As all resident and in transit ER proteins, sarcoglycans undergo a severe quality control check, and only the properly folded ones can assemble into a functional complex. Mutations, deletions and truncations in the polypeptide sequences rarely achieve the native structure. The consequence can be either a toxic gain of function because of aggregation, or a loss of function because of premature disposal of the unfolded/misfolded protein. The consequent disease is called protein-misfolded disease. On her studies, Dorianna Sandonà demonstrated that α-sarcoglycan mutants, being misfolded, are intercepted by the ER quality control system and prematurely degraded by the proteasome [Am. J. Path (2008) 173(1):170-81].
Currently, the main research interest of Dorianna Sandonà is the study of the ER-associated protein degradation (ERAD) pathways, responsible for the premature degradation of different mutated proteins of striated muscle. For example, she has recently revealed the route to degradation of the V247M mutant of α-sarcoglycan, the second most frequently reported mutant in LGMD2D [Hum Mol Genet. (2014) 23(14):3746-58]. Thanks to this successful research, she is now investigating the role of ERAD also in the premature degradation of mutated SERCA1 and calsequestrin-2 proteins, responsible for two other rare genetic diseases of striated muscles, such as Brody disease and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT).
In protein-misfolded diseases, large body of evidence indicates that frequently the muted protein is still functional, nevertheless it is rapidly degraded because folding-defective. From these premises, the other main purpose of Dorianna Sandonà is the development of novel therapeutic strategies to treat these diseases. Two different pharmacological interventions have been hypothesized. The first one, named “protein rescue” strategy, aims to reduce the degradation-rate of the mutants by acting on potential druggable targets of the degradative pathways. The second one, named “protein repair” strategy, intends to help the mutant-folding process, by using compounds known as pharmacological chaperones [Patent pending]. The successfully use in vitro of novel and existing small molecules has established the proof of concept of potential treatments for LGMD2D and Brody disease, for which no effective cure is now available.
Università di Padova