ALOISI FRANCESCA

Research themes
Multiple sclerosis: immunopathogenesis; lymphoid neogenesis; cortical damage.
Role of Epstein-Barr virus in multiple sclerosis and B-cell mediated autoimmune diseases. Search for compounds enhancing endogenous remyelination; TNF receptor signalling during demyelination and remyelination.
Astrocyte function at the blood-brain barrier in the healthy and diseased brain.

Keywords
Multiple sclerosis; immunopathogenesis; viral infection; remyelination; glial cells; microglia activation; TNF receptors; grey matter pathology; ion channels, blood-brain-barrier.

Methods
Analysis of post-mortem MS brain tissue; immunohistochemistry; laser capture microdissection; quantitative real time RT-PCR; oligodendrocyte progenitor cell and cerebellar organotypic cultures; cell biology techniques; immunoprecipitation, pull-down assays and co-purification procedures associated to MALDI-Tof analysis to identify protein-protein interactions in astrocytes; generation and functional characterization of astrocytoma cell lines stably overexpressing ion channels.

Composition of the research group

Cristina Agresti, Senior Research Scientist: coordination of studies on remyelination and TNF receptor signaling.

Elena Ambrosini, Research Scientist: coordination of studies on the role of astrocytes at the blood-brain barrier

Maria Stefania Brignone, Post-doctoral fellow, biochemistry of ion channels, protein interaction experiments, gene expression analysis.

Cecilia Eleuteri, PhD student, studies in in vitro and ex vivo mouse models of oligodendrocyte differentiation and remyelination; gene expression analysis; immunohistochemistry.

Angela Lanciotti, Post-doctoral fellow, generation of astrocytoma cell lines and primary rat astrocyte cultures, astrocyte transfection, immunohistochemistry in murine and human brain tissue.

Roberta Magliozzi, Contract Researcher, coordination of studies on cortical grey matter pathology in MS; gene expression analysis, immunohistochemistry.

Barbara Rosicarelli, Technician, neuropathological characterization of MS brain tissue samples; laser capture microdissection; immunohistochemistry.

Recent publications

1. Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol. 2009;22:201-6.



2. Veroni C, Gabriele L, Canini I, Castiello L, Coccia E, Remoli ME, Columba-Cabezas S, Aricò E, Aloisi F, Agresti C. Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways. Mol Cell Neurosci. 2010;45:234-244



3. Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds R. A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010;68:477-493.



4. Cavalcante P*, Serafini B*, Rosicarelli B, Maggi L, Barberis M, Antozzi C, Berrih-Aknin S, Bernasconi P, Aloisi F§, Mantegazza R§. Epstein-Barr virus persistence and reactivation in myasthenia gravis thymus. Ann Neurol 2010;67:726-38.*Equal contribution; §equal credit for senior authorship.



5. Serafini B, Columba-Cabezas S, Severa M, Rosicarelli B, Veroni C, Chiappetta G, Magliozzi R, Reynolds R, Coccia E, Aloisi F. Expression of Epstein-Barr virus latent membrane protein 2A and BAFF in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation. J Neuropathol Exp Neurol. 2010;69:677-693.



6. Aloisi F, Serafini B, Magliozzi R, Howell OW, Reynolds R Detection of Epstein-Barr virus and B-cell follicles in the multiple sclerosis brain: what you find depends on how and where you look. Brain. 2010;133(Pt 12):e157. Epub 2010 Aug 25.



7. Lanciotti A, Brignone MS, Camerini S, Serafini B, Macchia G, Raggi C, Molinari P, Crescenzi M, Musumeci M, Sargiacomo M, Aloisi F, Petrucci TC, Ambrosini E. MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiol. Dis. 2010;37:581-595.



8. Annibali V, Ristori G, Angelini DF, Serafini B, Mechelli R, Cannoni S, Romano S, Paolillo A, Abderrahim H, Diamantini A, Borsellino G, Aloisi F, Battistini L, Salvetti M. CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis. Brain 2011;134:542-554.



9. Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, Serafini B, Aloisi F, Roncaroli F, Magliozzi R, Reynolds R. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011;134:2755-2771.
   
   
10. Lassmann H, Niedobitek G, Aloisi F, Middeldorp JM; NEUROPROMISE EBV Working Group. Epstein-Barr virus in the multiple sclerosis brain: a controversial issue--report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain. 2011;134:2772-2786.
    
    
11. Serafini B, Cavalcante P, Bernasconi P, Aloisi F, Mantegazza R. Epstein-Barr virus in myasthenia gravis thymus: a matter of debate. Ann Neurol. 2011;70:519. doi: 10.1002/ana.22544.
    
    
12. Sundqvist E, Sundström P, Lindén M, Hedström AK, Aloisi F, Hillert J, Kockum I, Alfredsson L, Olsson T. Epstein-Barr virus and multiple sclerosis: interaction with HLA. Genes Immun. 2012;13:14-20. doi: 10.1038/gene.2011.42.
    
    
13. Brignone MS, Lanciotti A, Macioce P, Macchia G, Gaetani M, Aloisi F, Petrucci TC, Ambrosini E. The beta1 subunit of the na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: New insights into MLC pathogenesis. Hum. Mol. Genet. 2011;20:90-103.
    
    
14. Lanciotti A, Brignone MS, Molinari P, Visentin S, De Nuccio C, Macchia G, Aiello C, Bertini E, Aloisi F, Petrucci TC, Ambrosini E. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum. Mol. Genet. 2012;21:2166-2180.
    
    
15. Sundqvist E, Sundström P, Lindén M, Hedström AK, Aloisi F, Hillert J, Kockum I, Alfredsson L, Olsson T. Lack of replication of interaction between EBNA1 IgG Ab and smoking in risk for multiple sclerosis. Neurology 2012;79:1363-1368.
    
    
16. Choi SR, Howell OW, Carassiti D, Magliozzi R, Gveric D, Muraro PA, Nicholas R, Roncaroli F, Reynolds R. Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis. Brain. 2012;135:2925-2937.
    
    
17. Croia C*, Serafini B*, Bombardieri M, Humby F, Kelly S, Severa M, Rizzo F., Coccia E, Migliorini P, Aloisi F§, Pitzalis C§. Epstein-barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann Rheum Dis, 2012 December 25 [Epub ahead of print]. * Equal contribution; §equal credit for senior authorship.
    
    
18. Serafini B, Muzio L, Rosicarelli B, Aloisi F. Radioactive in situ hybridization for EBER supports presence of Epstein-Barr virus in the multiple sclerosis brain. Brain. 2013 Jan 25; doi: 10.1093/brain/aws315.
    
    
19. Magliozzi R, Serafini B, Rosicarelli B, Chiappetta G, Veroni C, Reynolds R, Aloisi F. B-cell enrichment and Epstein-Barr virus infection in inflammatory cortical lesions in secondary progressive multiple sclerosis. J Neuropathol Exp Neurol. 2013;72:29-41.
    
    
20. Angelini DF, Serafini B, Piras E, Severa M, Coccia EM, Rosicarelli B, Ruggieri S, Gasperini C, Buttari F, Centonze D, Mechelli R, Salvetti M, Borsellino G, Aloisi F*, Battistini1 L*. Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis. PloS Pathogens 2013, in press. *Equal credit for senior authorship.