Nata a Genova il 7 febbraio 1985, mi sono laureata in Medicina e Chirurgia nel 2009 presso l’Università degli Studi di Genova con una tesi sperimentale sul ruolo antiinfiammatorio delle cellule staminali mesenchimali nella Sclerosi Multipla. Ho svolto la mia formazione post-laurea all’IRCCS Ist. Neurologico C. Besta di Milano (U.O. Neuroimmunologia e Mal. Neuromuscolari) portando costantemente avanti l’attività di ricerca di base, parallelamente alla formazione clinica; nel 2016 mi sono specializzata in Neurologia presso l’Università di Milano Bicocca (UNIMIB) con una tesi sui microRNA coinvolti in una patologia giovanile del motoneurone. Come medico ricercatore il mio scopo è fare da ponte tra la ricerca di base e la sua applicazione clinica. Alla luce di questo, da ottobre 2015 ho iniziato il Dottorato in Neuroscienze presso UNIMIB e, da ottobre 2016, frequento il Jefferson ALS Weinberg Center, Thomas Jefferson University, Philadelphia (Pennsylvania). Qui, sotto la guida della Prof.ssa Piera Pasinelli, sto imparando a sviluppare nuovi modelli cellulari paziente-specifici per lo studio della Sclerosi Laterale Amiotrofica.

PROGETTO DI RICERCA

FM19G11 for the treatment of ALS in the G93A-SOD1 mouse model by promoting stem cell-mediated spinal cord regeneration

• Curriculum: Neuroscienze Sperimentali
• Tutor: Renato Mantegazza

Amyotrophic lateral sclerosis (ALS) is a fatal untreatable disease caused by motor neuron (MN) degeneration in motor cortex, brainstem and spinal cord. Two forms of ALS are recognized: sporadic (SALS) and familial (FALS), both characterized by similar pathological alterations. 20% of FALS are due to mutations in the SOD1 gene. The G93A-SOD1 mouse over-expresses the human mutated SOD1 gene and presents clinical symptoms and neuropathological features that mimic those of FALS.  

The vulnerability of MN cells arises from a combination of several mechanisms, such as protein misfolding and aggregation, mitochondrial dysfunction, oxidative damage, defective axonal transport, excitotoxicity, and impaired non-neuronal neighboring cells (e.g. astrocytes, microglia, muscle cells) influence. Among all these effectors, there is still no clear definition about which are the primary or secondary players, and the key question about therapeutic interventions remains mostly unresolved.

My project stems from Dr. Moreno-Manzano work about the recently identified compound FM19G11 which showed neuroprotective properties, by preserving neuronal tissue and reducing astroglial reaction in a spinal cord injury (SCI) model. Importantly, in vivo administration of FM19G11 significantly favored functional locomotion recovery in the SCI acute model. The mechanism of action of FM19G11 is related to its metabolic effect by increasing ATP synthesis and improving survival rates of ependymal stem progenitor cells (epSPCs) derived from spinal cord. When epSPCs are activated either by FM19G11 or by the inflammatory mediators, they show a better life-span and an improved MN differentiation rate.

Our group has developed a cell culture model deriving epSPCs from G93A-SOD1 spinal cord.

My project aims are: 1.To investigate in vitro FM19G11 effect on ALS G93A-SOD1-derived epSPCs, focusing on the molecular mechanisms involved in survival rate of stem cells and their MN differentiation rate. 2. To evaluate the efficacy of FM19G11 in modifying the disease progression by fostering MN regeneration in G93A-SOD1 mice; 3. To compare different routes of administration of the FM19G11 compound for the delivery in G93A-SOD1 mice; 4. To define FM19G11 mechanisms of action on stem-cell regeneration in G93A-SOD1 mice al different time points of treatment.

PERIODI ALL’ESTERO

Nel contesto del programma di dottorato, e del progetto di mobilità internazionale Exchange Extra-UE previsto da Bicocca per esperienze al di fuori dell’Europa, da ottobre 2016 ho iniziato a lavorare nel laboratorio e nella clinica multidisciplinare SLA del “ALS Weinberg Center”, alla Thomas Jefferson University di Philadelphia (Pennsylvania). Qui, sotto la supervisione della Prof. Piera Pasinelli, sto imparando a sviluppare nuovi modelli in vitro paziente-specifici con l’obiettivo di migliorare la comprensione dei meccanismi alla base della SLA, e sviluppare terapie orientate all’individuo.

PUBBLICAZIONI E CONGRESSI RECENTI

Pubblicazioni

• Brenna G, Antozzi C, Montomoli C, Baggi F, Mantegazza R; INCB-MG Group. “A propensity score analysis for comparison of T-3b and VATET in myasthenia gravis.” Neurology. 2017 Jun 7.
• Marcuzzo S, Bonanno S, Figini M, Scotti A, Zucca I, Minati L, Riva N, Domi T, Fossaghi A, Quattrini A, Galbardi B, D’Alessandro S, Bruzzone MG, García-Verdugo JM, Moreno-Manzano V, Mantegazza R, Bernasconi P. “A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis.” Exp Neurol. 2017 Jul;293:43-52.
• Colleoni L, Galbardi B, Barzago C, Bonanno S, Franzi S, Frangiamore R, Camera G, Foti M, Biancolini D, Canioni E, Maggi L, Antozzi C, Mantegazza R, Bernasconi P, Kapetis D. “A novel ABCC6 haplotype is associated with azathioprine drug response in myasthenia gravis.” Pharmacogenet Genomics. 2016 Dec 2.
• Figini M, Scotti A, Marcuzzo S, Bonanno S, Padelli F, Moreno-Manzano V, García-Verdugo JM, Bernasconi P, Mantegazza R, Bruzzone MG, Zucca I. “Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model.” PLoS One. 2016 Aug 25;11(8):e0161646.
• Barzago C, Lum J, Cavalcante P, Srinivasan KG, Faggiani E, Camera G, Bonanno S, Andreetta F, Antozzi C, Baggi F, Calogero RA, Bernasconi P, Mantegazza R, Mori L, Zolezzi F. “A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients.” Immunobiol. 2016, S0171-2985(16)30099-7.
• Sassone J, Taiana M, Lombardi R, Porretta C, Freschi M, Bonanno S, Marcuzzo S, Caravello F,  Caterina B, Lauria Pinter G. “ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin.” Hum Mol Genet.
• Cavalcante P, Galbardi B, Franzi S, Marcuzzo S, Barzago C, Bonanno S, Camera G, Maggi L, Kapetis D, Andreetta F, Biasiucci A, Motta T, Giardina C, Antozzi C, Baggi F, Mantegazza R, Bernasconi P. “Increased expression of Toll-like receptors 7 and 9 in myasthenia gravis thymus characterized by active Epstein-Barr virus infection.” Immunobiol. 2016, 221: 516-27.
• Marcuzzo S*, Bonanno S*, Kapetis D, Barzago C, Cavalcante P, D’Alessandro S, Mantegazza R, Bernasconi P. ” Up-regulation of neural and cell cycle-related microRNAs in brain of amyotrophic lateral sclerosis mice at late disease stage.” Mol Brain. 2015, 8: 5. * Equally contributed.
• Giordano A, Lugaresi A, Confalonieri P, Granella F, Radice D, Trojano M, Martinelli V, Solari A; SIMS-Practice group collaborator. “Implementation of the ‘Sapere Migliora’ information aid for newly diagnosed people with multiple sclerosis in routine clinical practice: a late-phase controlled trial.” Mult Scler. 2014 Aug;20(9):1234-43.
• Marcuzzo S, Kapetis D, Mantegazza R, Baggi F, Bonanno S, Barzago C, Cavalcante P, Kerlero de Rosbo N, Bernasconi P. “Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells.” Exp Neurol. 2013, 253: 91-101.
• Marcuzzo S, Zucca I, Mastropietro A, de Rosbo NK, Cavalcante P, Tartari S, Bonanno S, Preite L, Mantegazza R, Bernasconi P. “Hind limb muscle atrophy precedes cerebral neuronal degeneration in G93A-SOD1 mouse model of amyotrophic lateral sclerosis: a longitudinal MRI study.” Exp Neurol. 2011, 231: 30-37.
• Mantegazza R, Bonanno S, Camera G, Antozzi C. “Current and emerging therapies for the treatment of myasthenia gravis.” Neuropsychiatric Dis Treat. 2011, 7: 151-160.
• Uccelli A, Morando S, Bonanno S, Bonanni I, Leonardi A, Mancardi G. “Mesenchymal stem cells for multiple sclerosis: does neural differentiation really matter?” Curr Stem Cell Res Ther. 2011, 6: 69-72.

Congressi

• Altered expression patterns of neural- and cell cycle-related miRNAs and their predicted target genes in G93A-SOD1 mouse brain regions. Bonanno S, Marcuzzo S, Barzago C, Cavalcante P, Kapetis D, Bernasconi P and Mantegazza R. Poster Presenter at Federation European Neuroscience Society (FENS) Forum Congress. Milan 2014.
• Diffusion magnetic resonance imaging: a promising novel tool for early detection and monitoring of motor neuron degeneration in ALS. Marcuzzo S, Moreno-Manzano V, Zucca I, Bigini M, Scotti A, Bonanno S, Galbardi B, Kapetis D, Bernasconi P and Mantegazza R. Poster Presenter at International Congress on Neuromuscular Diseases (ICNMD). Nice 2014.
• Neural stem cell activation in the subventricular zone and hippocampus of G93A-SOD1 mice: the microRNA up-regulation. Bonanno S, Marcuzzo S, Barzago C, Cavalcante P, Kapetis D, Bernasconi P and Mantegazza R. Poster Presenter at Congresso Nazionale Società Italiana di Neuroscienze (SINS). Roma 2013.

ALTRE INFO

Per accedere ad ulteriori informazioni visita:

• il sito ORCID
• la pagina personale ResearchGate