“Pathogenetic mechanism of Limb Girdle Muscular Dystrophy 1F/D2: functional characterization of Transportin 3 in cellular and animal models of disease”
The project is aimed to clarify pathogenesis of LGMD1F/D2 and the relationship with mutated mutTPNO3 gene. Genetic analysis identified a deletion in the stop codon of TNPO3 that encodes for an importin that transports proteins involved in splicing and mRNA metabolism. It is unclear how mutTNPO3 induces clinicopathological features of LGMD1F/D2. Our hypothesis is that mutated protein is unable to carry its cargo to the nucleus causing disorders in RNA metabolism (i.e altered myogenesis and myofibrillar disarray) likely leading to protein aggregates and autophagy (cell atrophy and weakness in LGMD1F/D2). A cDNA sequence of mutTNPO3 will be transfected in both hSCs and C2C12 cell cultures and microinjected in Zebrafish embryos to analyze the effect of mutTNPO3 on myogenesis and on the expression of myofibrillar proteins, markers of autophagy and atrophy, TNPO3 cargoes and proteins involved in its pathway. in silico model will be explored to identify new targets-TPNO3 related.
Inflammatory Myopathies: diagnostic test validation using immunohistochemical reaction for MHC-I, major histocompatibility antigen class I,localization. The study is focused on the relationship between stress induced modifications of sarcoplasmic reticulum and the expression of MHC-I at both sarcoplasmic and sarcolemmal site as evidenced by immunohistochemical studies.Submicroscopical myocyte alteration are described by transmission electron microscopic analysis. Moreover, proteomic analysis is performed to define all stress-induced proteins involved in the pathogenetic mechanisms of inflammatory myopathies.
Inflammatory Myopathies:miRNA expression study in exosome vesicles as a possible diagnostic marker in the differential diagnosis among inflammatory myopathies focusing on Inclusion Body Myopathy, IBM
Inflammatory Myopathies:miRNA expression study in exosome vesicles as a possible diagnostic marker in the differential diagnosis among inflammatory myopathies focusing on Inclusion Body Myopathy, IBM
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