Claudia Malacarne

Curriculum Vitae

Born on October 17th, 1992, I earned my BS in Biological Science in 2016 and my MS in Biology in 2018 at the University of Milano Bicocca. I carried out my internship at the Neuroimmunology and Neuromuscular Diseases Unit of Istituto Neurologico Carlo Besta in Milan with a master thesis on the involvement of muscle-specific microRNAs (myomiRs) in motor neuron disease (MND) animal models during disease pathogenesis and progression. In 2018 I was able to continue my research in the same Unit first as a visiting researcher and then as a junior research fellow. 

In 2019 I was enrolled in the PhD program of Experimental Neuroscience at the University of Milano-Bicocca. Under the supervision of Dr. Renato Mantegazza my research project will investigate the myomiR role in human iPSC-derived skeletal muscle fibers from ALS patients.

Research Project

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

  • Track: Experimental Neuroscience
  • 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.

Publications and congresses partecipation

 Publications

  • 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

Congresses

  • (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). 

Further info

 

Elisabetta Donzelli
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