Pathophysiology of Striated Muscles
Our group studies the cellular and molecular mechanisms underlying selected pathologies of cardiac and skeletal muscles with the aim to identify and develop novel therapeutic strategies to fight these rare diseases.Our efforts are devoted to clarify the pathogenic consequences of protein misfolding in sarcoglycanopathy, Brody disease and catecholaminergic polymorphic ventricular tachycardia (CPVT). For this reason we are developing innovative platforms useful for studying rare muscular diseases at the basal level and for drug screening and validation. This approach may be helpful for translating therapeutic strategies from one pathology to another.
We are also interested in understanding the molecular basis driving cardiac growth and the impact of these processes on the development of congenital and adult cardiovascular diseases. The study of heat stroke and of skeletal muscle atrophy as consequence of disuse (microgravity, ageing and bed rest) are two other topics of our group. To accomplish these tasks, we use cellular models, primary myogenic cells from healthy and affected subjects as well as mouse and zebrafish models of the diseases.
People
Faculty
- Pompeo VOLPE - Associate Professor
- Marina CAMPIONE - C.N.R. Senior Scientist
- Marta MURGIA - Assistant Professor
- Alessandra NORI - Assistant Professor
- Dorianna SANDONA' - Associate Professor
Lab Member
- Martina SCANO - Post-doctoral fellow
- Francesco DALLA BARBA - Research fellow
- Barbara RAVARA - Research fellow
- Giorgia VALLE - Research fellow
- Sandra FURLAN - C.N.R. Senior Technician
- Alberto BENETOLLO - PhD Student
- Paola CACCIN - Research assistant
- Marcello CAROTTI - Research assistant
Five recent publications
- Scano M, Benetollo A, Nogara L, Bondì M, Barba FD, Soardi M, Furlan S, Akyurek EE, Caccin P, Carotti M, Sacchetto R, Blaauw B, Sandonà D.
CFTR corrector C17 is effective in muscular dystrophy, in vivo proof of concept in LGMDR3.
Hum Mol Genet. 2021 Sep 9:ddab260. doi: 10.1093/hmg/ddab260 - Carotti M, Scano M, Fancello I, Richard I, Risato G, Bensalah M, Soardi M, Sandonà D. Combined Use of CFTR Correctors in LGMD2D Myotubes Improves Sarcoglycan Complex Recovery. Int J Mol Sci. 2020 Mar 6;21(5):1813. doi: 10.3390/ijms21051813.
- Carotti M, Marsolier J, Soardi M, Bianchini E, Gomiero C, Fecchio C, Henriques SF, Betto R, Sacchetto R, Richard I, Sandonà D. Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for Limb Girdle Muscular Dystrophy 2D. Hum Mol Genet. (2018) 27(6):969-984
- Furlan S, Mosole S, Murgia M, Nagaraj N, Argenton F, Volpe P, Nori A. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio. J Muscle Res Cell Motil. 2016 Apr;37(1-2):27-39.
- Piroddi N, Pesce P, Scellini B, Manzini S, Ganzetti GS, Badi I, Menegollo M, Cora V, Tiso S, Cinquetti R, Monti L, Chiesa G, Bleyl SB, Busnelli M, Dellera F, Bruno D, Caicci F, Grimaldi A, Taramelli R, Manni L, Sacerdoti D, Tesi C, Poggesi C, Ausoni S, Acquati F, Campione M. Myocardial overexpression of ANKRD1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovasc Res. 2020;116(8):1458-1472.
- Liu B, Walton SD, Ho HT, Belevych AE, Tikunova SB, Bonilla I, Shettigar V, Knollmann BC, Priori SG, Volpe P, Radwański PB, Davis JP, Györke S. Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia. J Am Heart Assoc. (2018) 7(10). pii: e008155. doi: 10.1161/JAHA.117.008155.
Projects
- Italian Telethon (PI Sandonà): “3D modelling of rare muscular diseases, a powerful platform for basic studies and drug validation”, 2021-2024
- Italian Telethon (PI Sandonà) Seed Grant Spring 2020 MCT8: "Repurposing CFTR correctors in Allan Herndon Dudley syndrome" 2021-2022
- AFM (Association française contre les myopathies) (PI Sandonà): “CFTR correctors to treat sarcoglycanopathy, a repurposing story” 2020-2022
- MDA (Muscular dystrophy association) (PI Sandonà): “Novel zebrafish models of sarcoglycanopathy. Swimming toward a cure.” 2018-2021
- Programma PoC@Unipd (PI Sandonà): Recuperare proteine misfolded di malattie rare grazie a molecole note (Rimedio) 2021-2022
- ASI (Agenzia Spaziale Italiana) (PI Volpe): Microgravity-induced gene expression in a nerve-muscle coculture model (NeMuCo) 2018-2021
- BIRD (PI A. Nori ): Exploring Calsequestrin-based Calcium stores in mammalian cerebellum
Useful links
Rare diseases:
- Sandonà D., Betto R. Sarcoglycanopathies: molecular pathogenesis and therapeutic prospects. Expert. Rev. Mol. Med. (2009) Sep 28; 11:e28
- Carotti M., Fecchio C., Sandonà D. Emerging therapeutic strategies for sarcoglycanopathy. Exp Opin in Orphan drugs. (2017) 5(5): 381-396
- Valle G, Galla D, Nori A, Priori SG, Gyorke S, de Filippis V, Volpe P. Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin. Biochem J. (2008) 413(2):291-303.
Pathogenic consequences of protein misfolding:
- Bianchini E., Testoni S., Gentile A., Calì T., Ottolini D., Villa A., Brini M., Betto R., Mascarello F., Nissen P., Sandonà D.*, Sacchetto R.* Inhibition of Ubiquitin Proteasome System Rescues the Defective Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA1) Protein Causing Chianina Cattle Pseudomyotonia. J Biol Chem. (2014) 289(48):33073-82
- Gastaldello S., D’Angelo S., Franzoso S., Fanin M., Angelini C., Betto R., Sandonà D. Inhibition of proteasome activity promotes the correct localization of disease-causing α-sarcoglycan mutants in a heterologous cell system constitutively expressing β-, γ-, and δ-sarcoglycan. Am. J. Path (2008) 173(1):170-81
Molecular basis driving cardiac growth:
- Campione M, Franco D. Current Perspectives in Cardiac Laterality. J Cardiovasc Dev Dis. 2016 Dec 9;3(4).
- Ammirabile G, Tessari A, Pignataro V, Szumska D, Sardo FS, Benes J Jr, Balistreri M, Bhattacharya S, Sedmera D, Campione M.(2012). Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium. Cardiovasc Res. 93,291-230.
- Tessari A, Pietrobon M, Notte A, Cifelli G, Gage PJ , Schneider MD, Lembo G, Campione M.(2008). Myocardial Pitx2 differentially regulates the left atrial identity and ventricular asymmetric remodelling programs. Circ. Res 102,813-822.
Skeletal muscle atrophy:
- Mosole S, Zampieri S, Furlan S, Carraro U, Löefler S, Kern H, Volpe P, Nori A. Effects of Electrical Stimulation on Skeletal Muscle of Old Sedentary People. Gerontol Geriatr Med. (2018) Apr 10; 4:2333721418768998
- Gambara G, Salanova M, Ciciliot S, Furlan S, Gutsmann M, Schiffl G, Ungethuem U, Volpe P, Gunga HC, Blottner D. Gene Expression Profiling in Slow-Type Calf Soleus Muscle of 30 Days Space-Flown Mice. PLoS One. (2017) 12(1):e0169314.
- Sandonà D, Desaphy JF, Camerino GM, Bianchini E, Ciciliot S, Danieli-Betto D, Dobrowolny G, Furlan S, Germinario E, Goto K, Gutsmann M, Kawano F, Nakai N, Ohira T, Ohno Y, Picard A, Salanova M, Schiffl G, Blottner D, Musarò A, Ohira Y, Betto R, Conte D, Schiaffino S. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. PLoS One. (2012) 7(3):e33232
Mouse and zebrafish models of the diseases:
- Valle G, Boncompagni S, Sacchetto R, Protasi F, Volpe P. Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia. Exp Cell Res. (2014) 321(2):178-89
- Valle G, Vergani B, Sacchetto R, Reggiani C, De Rosa E, Maccatrozzo L, Nori A, Villa A, Volpe P. Characterization of fast-twitch and slow-twitch skeletal muscles of calsequestrin 2 (CASQ2)-knock out mice: unexpected adaptive changes of fast-twitch muscles only. J Muscle Res Cell Motil. (2016) 37(6):225-233.
- Furlan S, Mosole S, Murgia M, Nagaraj N, Argenton F, Volpe P, Nori A. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio. J Muscle Res Cell Motil. 2016 Apr;37(1-2):27-39.
