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Born in 1964 in Horgen (Switzerland), Dorianna Sandonà graduated in 1988 in Biological Sciences from the University of Padua and received her doctorate in Pathology and molecular and cellular biology in 1994. She completed her post-doc at the University of Verona, returning to Padua in 1998. She is married to Francesco Di Virgilio.
With her research group she has been studying for years the pathological mechanisms of rare genetic diseases that affect the striated muscles, in particular sarcoglycanopathies. She patented the use of small molecules developed to treat cystic fibrosis, as a new possible therapy for some of muscular diseases. Many of her projects have been funded by national and international foundations (Telethon, MDA, AFM); actively collaborates with various European research groups.
Presently, Dorianna Sandonà works on the development of new therapeutic approaches oriented to the treatment of rare diseases. This efforts is based on the definition at the molecular level of the pathogenetic mechanisms, which can be similar even in very different pathologies and the creation of innovative disease models.
· 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
· 2008-2014: course of Molecular Biology II Laurea Magistrale in Biotecnologie Farmaceutiche University of Padova
· 2014 - to date: course of Advanced Molecular Biology, Master degree Pharmaceutical Biotechnologies
· 2016 - to date: course of Protein Engineering, Master degree Pharmaceutical Biotechnologies
· 2017 - 2018: 1 CFU in the course of Molecular Biology, Master degree in Medicine and Surgery
· 2018 – to date: 2 CFU in the course of Molecular Biology, Master degree in Medicine and Surgery
The common goal that connects all the research lines coordinated by Prof. Sandonà is the search for new therapies for the treatment of rare genetic diseases. This implies understanding in depth the molecular mechanisms at the bases of the disease; developing suitable study models; screening and validating potential drugs, translating the most promising ones toward preliminary clinical studies.
Sarcoglycanopathies are the first diseases that Prof Sandonà has dealt with since the 2000s; they are muscular dystrophies belonging to the Limb Girdle Muscular Dystrophies (LGMD). They are caused by mutations in the genes coding for sarcoglycans, transmembrane proteins that, organized in tetramer, participate in the formation of the major dystrophin complex, essential for the connection of the contractile apparatus, inside the muscle fibers, with the extracellular matrix. In sarcoglycanopathies, mutations lead to the disruption of the tetramer with the consequent damage of the plasma membrane and the progressive muscle degeneration (Kirschner J, Lochmuller H 2011 DOI: 10.1016/B978-0-08-045031-5.00003-7)
In particular, the studies conducted on alpha-sarcoglycan allowed understanding the physio/pathological mechanism by which these proteins are synthesized, scrutinized by the cell quality control for correctness, assembled and eventually delivered at the plasma membrane. Often, when mutated, sarcoglycans are not correctly folded and are therefore eliminated by the ubiquitin-proteasome system, even if potentially functional (Sandonà and Betto 2009 doi: 10.1017/S1462399409001203)
Similar mechanisms are observed in other pathologies (Cystic fibrosis, Brody myopathy, CPVT syndrome), defined as protein misfolding diseases. Preventing the cells from eliminating misfolded proteins could allow to recover enough functional protein to restore the healthy phenotype. Current work is therefore mainly devoted towards the search and use of small molecules, designed ad hoc or already used for other purposes, which acting at different levels may block or slow down the pathological mechanisms. To this intent, developing disease models to significantly and quickly assess the large number of potentially active molecules is another significant part of the laboratory's work. In particular:
In vitro models: heterologous as well primary patient cells and, in some cases, pathological immortalized cell lines deriving from the primary ones represent versatile tools for first screening of compounds, as well as for basic studies (Carotti et al 2018 doi: 10.1093/hmg/ddy013; Carotti et al 2020 doi: 10.3390/ijms21051813)
3D reconstruction of muscle tissue: to reproduce in vitro the complexity of muscle tissue, Prof Sandonà's group is developing, thanks to Telethon funding (link to the page), three-dimensional culture systems of healthy and pathological muscle cells.
In vivo model, zebrafish: the zebrafish genome was modified using the CRISPR/Cas9 technique to replicate some of the pathological mutations of sarcoglycans
In vivo model, humanized mouse: to overcome the lack of phenotype of the conventional KI animals of sarcoglycanopathy (Bartoli et al 2008 doi: 10.1093/hmg/ddn029; Kobuke et al 2008 doi:10.1093/hmg/ddn009; Henriques et al 2018 doi: 10.1371/journal.pone.0191274), new-born alpha-sarcoglycan null mice are injected in the hind-limbs with viral vectors expressing the mutated version of the human protein. Adult animals, well resembling the human phenotype, are suitable for the systemic administration of potential drugs thus evaluating the functional recovery of the phenotype
The research of Prof Sandonà resulted in patents protecting the novel use of small molecules called CFTR correctors for the treatment of rare muscle diseases such as sarcoglycanopathies, Brody disease and CPVT.
- Italian patent 0001414647 (2015),
- US patent 9,987,256 B2 (2018),
- European patent: EU 2925317 (2019),
- PCT/EP2019/050585 (pending).
The idea of exploiting similar approaches in different pathologies resulted in the recent funding of a new project concerning the repurposing of the CFTR correctors in Allan Herndon Dudley syndrome.
Another field of interest is the structural study of the sarcoglycan complex, to deepen the knowledge about its physio-pathological role in striated muscle and to possibly design new molecules for therapeutic purposes.
Dr. Isabelle Richard, Laboratory of Progressive Muscular Dystrophies, Genethon, Evry, France
Prof. Urlich Schweiz, Institute of Biochemistry and Molecular Biology, Bonn center for Neurosciences University of Bonn, Germany
Dr. Vincent Mouly, Platform for cell immortalization, Center Of Research In Myology, Sorbonne University – INSERM, Paris, France
Dr. Martina Piccoli, Laboratorio Ingegneria Tissutale Fondazione istituto di Ricerca Pediatrica, Città della Speranza, Padova, Italy
Dr. Cesare Gargioli, Laboratorio di Anatomia Comparata e Ingegneria Tissutale Università di Roma 2, Italy
Prof. Sandonà is firmly convinced of the importance of sharing knowledge about scientific research, particularly with children and teenagers. Together with her group, she carries out various activities to make everyone understand the importance of scientific research and to raise awareness about the issue of rare diseases.
Below are some of the activities carried out in recent years.
- 2021 The lab has become “Friend of rare Disease Day”
In collaboration with ICTea https://www.youtube.com/c/ICTea, “Di ricerca e.. principesse” (https://youtu.be/HRN7q3MTsxE)
- 2014-2019 Presentation for students of the secondary school: “Progetto di orientamento alle facoltà scientifiche: Ricerca I love you”
- 2018 Kids University “ Muscle games: multiple ability to create a drug”