Claudia Malacarne

Claudia Malacarne

Curriculum Vitae

Nata a Milano il 17 Ottobre 1992, nel 2016 ho conseguito la Laurea Triennale in Scienze Biologiche e nel 2018 la Laurea Magistrale in Biologia presso l’Università degli Studi di Milano Bicocca. La mia tesi finale, svolta nel laboratorio della U.O. di Neuroimmunologia e Malattie Neuromuscolari dell’Istituto Neurologico Carlo Besta, ha riguardato lo studio, in modelli murini, del ruolo dei microRNA muscolari (myomiRs) nella patogenesi e nella progressione delle malattie del motoneurone. Dal 2018 ho avuto la possibilità di continuare la mia ricerca nello stesso laboratorio, prima come Visiting Researcher e successivamente come borsista. Dal novembre 2019 frequento il dottorato di ricerca in Neuroscienze e sotto la supervisione del Dottor Renato Mantegazza presso l’Istituto Neurologico Carlo Besta mi dedicherò allo studio del ruolo dei myomiRs in cellule muscolari derivanti da iPSCs di pazienti con malattie del motoneurone.

Progetto di Ricerca

Unraveling the role of microRNAs and their target genes in amyotrophic lateral sclerosis: towards the identification of novel therapeutic targets

  • Curriculum: Neuroscienze Sperimentali
  • Tutor: Renato Mantegazza

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons of brainstem, motor cortex and spinal cord which leads to muscle atrophy, paralysis and eventually death. In most cases, ALS occurs as a sporadic disease (sALS), while about 10% of patients suffer from the familial form (fALS). Genetic mutations are known to cause fALS and the most common are located in the SOD1, C9ORF72, FUS and TDP-43 genes. 

In the last decades several studies highlighted a crucial role of skeletal muscle in ALS pathogenesis and progression, suggesting that muscle wasting is not only due to motor neuron death but also to changes in myocytes. 

At the same time microRNAs (miRNAs) have emerged as pivotal regulators of gene expression in a multiplicity of biological processes such as myogenic pathways and miRNA dysregulations are associated with many diseases.

Aim of the project drifts towards the identification of skeletal muscle disrupted mechanisms involving microRNAs underlying ALS pathogenesis and progression. 

To reach the goal we: 1) generate skeletal muscle in vitro model derived from human induced pluripotent stem cells (hiPSCs) of ALS patients and controls; 2) identify differentially expressed miRNAs and their target gene mRNAs in myoblasts derived from ALS patients and controls in order to select potential targets for novel therapeutic approaches; 3) test the efficacy of miRNAs as therapeutic targets by miRNA mimic and inhibitor administration in the novel generated in vitro model of hiPSC-derived skeletal muscle fibers, in a view of in vivo functional studies on ALS animal model.

Pubblicazioni e partecipazione a congressi

 Pubblicazioni

  • Bonanno S, Marcuzzo S, Malacarne C, Giagnorio E, Masson R, Zanin R, Arnoldi MT, Andreetta F, Simoncini O, Venerando A, Gellera C, Pantaleoni C, Mantegazza R, Bernasconi P, Baranello G, Maggi L. Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients. Biomedicines, January 2020 DOI: 10.3390/biomedicines8020021
  • Marcuzzo S, Isaia D, Bonanno S, Malacarne C, Cavalcante P, Zacheo A, Laquintana V, Denora N, Sanavio B, Salvati E, Andreozzi P, Stellacci F, Krol S, Mellado-López M, Mantegazza R, Moreno-Manzano V, Bernasconi P.FM19G11-Loaded Gold Nanoparticles Enhance the Proliferation and Self-Renewal of Ependymal Stem Progenitor Cells Derived from ALS Mice. Cells, March 2019 DOI: 10.3390/cells8030279
  • Marcuzzo S, Bonanno S, Barzago C, D’Alessandro S, Cavalcante P, Galbardi B, Malacarne C, Taiana M, Nizzardo M, Corti S, Bechi G, Gambardella A, Franceschetti S, Mantegazza M, Zorzi G, Mantegazza R, Bernasconi P. Revealing the involvement of miR-376a, miR-432 and miR-451a in infantile ascending hereditary spastic paralysis by microRNA profiling in iPSCs. Journal of Translational Science 2018 DOI:  10.15761/JTS.1000247

Partecipazione a congressi

  • (Poster)  Malacarne C., Marcuzzo S., Bonanno S., Meroni M., Poletti A., Galbiati M., Mantegazza R. and Bernasconi P, “Unraveling the role of muscle-specific microRNAs in the myogenic processes in ALS mice”, Focus on ALS / MND meeting Genova, Italy (September 2018). 

Altre informazioni

 

Elisabetta Donzelli
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