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Muscle biology and pathology

Muscular tissue represents the vast majority of the body, and many severe diseases, of both genetic and traumatic origin, involve cardiac and skeletal muscles. The IBCN projects in this research area concentrate on mechanisms regulating myo/pathogenesis at transcriptional and post-transcriptional levels, including epigenetic mechanisms altering chromatin organization. The ultimate goal of these different and integrated research interests is to develop novel strategies of regenerative medicine and muscle disease treatment, as well as innovative prognostic/diagnostic tools.

Specifically, the research lines focus on: 

  • generation of human cell and tissue models of cardiac and skeletal muscle pathologies through cell reprogramming (iPS) technology and murine models of ischemic events to develop cell therapy supported by innovative biomaterials 

  • studying the effect of histone deacetylase (HDAC) inhibitors and the contribution of macrophages in cardiac regeneration/remodelling and in muscular dystrophies 

  • refining the role of the tyrosin-kinase receptor c-Kit in cardiac repair after injury 

  • defining the role of regulatory genes (IFRD1 and cyclin D3) and associated molecular pathways in the control of  skeletal muscle stem cell function and muscle regeneration

  • validating zinc-finger based artificial transcription factors targeting utrophin gene promoter for treatment of Duchenne Muscular Dystrophy

  • identification of potentially pathogenetic microRNAs and target genes through analysis of microRNA-target interactions in muscle tissues from patients affected by Myotonic Dystrophy

  • investigating the DNA methylation patterns and histone marks of genes associated with the development of the Facioscapulohumeral Muscular Dystrophy

  • unraveling the mechanisms involved in interactions between chromatin and lamins/nuclear pore complexes in lamin-dependent muscular dystrophies

  • Characterization of nitric oxide role in the regulation of epigenetic enzymes and their contribution to the development of Duchenne Muscular Dystrophy associated cardiomyopathy

 

  • Personnel involved

  • Selected publications

Di Certo MG, Corbi N, Strimpakos G, Onori A, Luvisetto S, Severini C, Guglielmotti A, Batassa EM, Pisani C, Floridi A, Benassi B, Fanciulli M, Magrelli A, Mattei E, Passananti C.
The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice.
Hum Mol Genet. 2010; 19(5):752-760.
doi: 10.1093/hmg/ddp539.

Isidori AM, Cornacchione M, Barbagallo F, Di Grazia A, Barrios F, Fassina L, Monaco L, Giannetta E, Gianfrilli D, Garofalo S, Zhang X, Chen X, Xiang YK, Lenzi A, Pellegrini M, Naro F.
Inhibition of type 5 phosphodiesterase counteracts b2-Adrenergic signalling in beating cardiomyocytes.
Cardiovasc Res. 2015; 106(3):408-420.
doi: 10.1093/cvr/cvv123.

Bearzi C, Gargioli C, Baci D, Fortunato O, Shapira-Schweitzer K, Kossover O, Latronico MVG, Seliktar D, Condorelli G, Rizzi R. 
PlGF–MMP9-engineered cardiomyocyte-derived iPS cells supported on a PEG–fibrinogen hydrogel scaffold possess an enhanced capacity to repair damaged myocardium. 
Cell Death Dis. 2014; 5, e1053.
doi: 10.1038/cddis.2014.12.

Rizzi R, Di Pasquale E, Portararo P, Papait R, Cattaneo P, Latronico MVG, Altomare C, Sala L, Zaza A, Hirsch E, Naldini L, Condorelli G, Bearzi C.
Post-natal cardiomyocytes can generate iPS cells with an enhanced capacity toward cardiomyogenic re-differentation. 
Cell Death Differ. 2012; 19: 1162-1174.
doi: 10.1038/cdd.2011.205.

De Luca, G., Ferretti, R., Bruschi, M., Mezzaroma, E., Caruso, M.
Cyclin D3 critically regulates the balance between self-renewal and differentiation in skeletal muscle stem cells.
Stem Cells. 2013; 31: 2478–2491.
doi: 10.1002/stem.1487.

Micheli L, Leonardi L, Conti F, Maresca G, Colazingari S, Mattei E, Lira SA, Farioli-Vecchioli S, Caruso M, Tirone F.
PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kappaB.
J Biol Chem. 2011; 286(7):5691-5707.
doi: 10.1074/jbc.M110.162842.

Cesarini E, Mozzetta C, Marullo F, Gregoretti F, Gargiulo A, Columbaro M., Cortesi A, Antonelli L, Di Pelino S, Squarzoni S, Palacios D, Zippo A, Bodega B, Oliva G and Lanzuolo C.

Lamin A/C sustains PcG proteins architecture maintaining transcriptional repression at target genes.

J Cell Biol. 2015; 211(3):533-551. 
doi: 10.1083/jcb.201504035.

Falcone G, Perfetti A, Cardinali B, Martelli F. 

Noncoding RNAs: Emerging Players in Muscular Dystrophies
Biomed Res Int. 2014; 2014:503634.
doi: 10.1155/2014/503634.

Strimpakos G, Corbi N, Pisani C, Certo MG, Onori A, Luvisetto S, Severini C, Gabanella F, Monaco L, Mattei E, Passananti C.
Novel Adeno-Associated Viral Vector Delivering the Utrophin Gene Regulator Jazz Counteracts Dystrophic Pathology in mdx Mice.
J Cell Physiol. 2014; 229(9):1283-1291.


doi: 10.1002/jcp.24567.

BREVETTI


Brevetto dal titolo "Compositions and Methods for treating of Muscular Dystrophy“ International patent #PCT/EP2014/002051. 2014.
Titolarità CNR 100%. Ceduto in licensig esclusivo a Zingenix Ltd  (Israele).