farina.cinthia@hsr.it

The main focus of my lab is the study of the biological processes associated with multiple sclerosis. Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the loss of the myelin sheath surrounding the axons leading to alterations of the action potential propagation. It is presumably an autoimmune disease, as MS lesions present immune cell infiltration and the animal model of disease, the experimental autoimmune encephalomyelitis (EAE), is induced by immunization with myelin antigens. This leads to the activation of encephalitogenic T lymphocytes that enter the CNS, attack the myelin-forming cells (the oligodendrocytes) and start an inflammatory reaction that is amplified by CNS resident cells as the astrocytes and the microglia and by infiltrating immune cells. The currently used therapeutics for MS patients are immunosuppressive and immunomodulatory drugs, indicating that peripheral processes sustain disease. Thus, both central and peripheral events are involved in MS and need to be investigated. My scientific activity has been and is currently driven by a translational approach. Taking the moves from clinical observations and from human samples (blood or cerebral tissue), my research explores the activity of immune/glial/neuronal cells in vitro, goes to the in vivo mouse models, sums up the high-throughput generated data with systems biology approaches, until it is ready to go back to the clinic via the identification of novel diagnostic and prognostic biomarkers and the proposition of new therapeutic targets and approaches.

Curriculum Vitae

  • EDUCATION

1994    Doctor in Biological Sciences, major Molecular and Cellular Biology, from the University of Milan, Italy. Advisor: Prof. Sergio Ottolenghi; Coadvisor: Prof. Giorgio Parmiani.

1995   State examination for Biologists

2006 PhD in Human Biology, summa cum laude, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany. Advisor: Prof. Edgar Meinl

 

  • AWARDS

2005    Young Investigator Award for Multiple Sclerosis Research (1st prize), European Charcot Foundation.

2008 PhD Award among all Faculties, Ludwig-Maximilians-University, Munich.

  • PROFESSIONAL ACTIVITY

1992-1997       Department of Experimental Oncology, Tumor Immunology and Immunotherapy, directed by Dr. Giorgio Parmiani, at the National Institute of Cancer Research in Milan.

1998-2005     Department of Neuroimmunology, directed by Prof. Hartmut Wekerle, at the Max-Planck-Institute of Neurobiology and in collaboration with the Institute for Clinical Neuroimmunology directed by Prof. Reinhard Hohlfeld, Munich

2005-2010     Group Leader in the Department of Neuroimmunology at the Neurological Institute Carlo Besta, Milan, Italy. Brain Gain program financed by the Ministry for Health.

Nov 2010-present    Group Leader at INSpE, Division of Neuroscience, San Raffaele scientific Institute, Milan, Italy.

 

Research Activity

CNS Homeostasis and Pathology:

  • Neuroprotective vs neuroinflammatory role of astrocytes.
  • Interaction between glia and neuronal cells.
  • Neuroprotective properties of current MS therapeuticals.
  • Reactive glia in MS lesions
  • Analysis of appropriate transgenic animal models for the study of astrocyte reactivity in vivo

 

Multiple sclerosis pathogenesis

  • Contribution of Epstein Barr Virus to the autoimmune process leading to CNS demyelination.
  • Mechanisms of B cell persistance in CNS

 

Transcriptomics, bioinformatics and systems biology in Multiple sclerosis

  • Functional Genomics in Clinically Isolated Syndromes and MS.
  • Genetic and transcriptional protein networks in multiple sclerosis.
  • Functional annotation, target identification and validation.

 

Monitoring immunomodulatory therapies for multiple sclerosis

  • Pharmaco-transcriptomics and biomarker identification.

 

Basic Neuroimmunology: Interaction between nervous and immune system

  • Activation of immune cells by neurotrophic factors
  • Neurotrophins and T cell development and activation
  • Neurotrophic factors in skeletal muscle physiology and pathology

Publications

  1. Neuhaus O., Farina C., Yassouridis A., Wiendl H., Then Bergh F., Dose T., Wekerle H., Hohlfeld R. Multiple sclerosis: comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. N. A. S. 97(13): 7452, 2000.
  2. Farina C., Then Bergh F., Albrecht H., Meinl E., Yassouridis A., Neuhaus O., Hohlfeld R. Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-? response in blood cells. Brain 124, 2001.
  3. Farina, V. Vargas, N. Heydari, T. Kümpfel, E. Meinl, R. Hohlfeld. Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients. J. Neuroimmunol. 123, 2002.
  4. Farina, S. Wagenpfeil, R. Hohlfeld. Immunological assay for assessing the efficacy of glatiramer acetate in multiple sclerosis. J. Neurology 249, 2002.
  5. Farina, D. Theil, B. Semlinger, R. Hohlfeld and E. Meinl. Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokine. International Immunology 16 (6), 2004.
  6. S. Weber, M. Starck, S. Wagenpfeil, E. Meinl, R. Hohlfeld and C. Farina. Multiple sclerosis: Glatiramer Acetate inhibits monocyte reactivity in vitro and in vivo. Brain 127, 2004.
  7. Farina C., Krumbholz M., Giese T., Hartmann G., Aloisi F., Meinl E. Expression and function of Toll- like receptor 3 in human astrocytes. Neuroimmunol. 159, 2005.
  8. Farina, M.S. Weber, E. Meinl, H. Wekerle and R. Hohlfeld. Glatiramer Acetate (GLAT) in multiple sclerosis: Update on potential mechanisms of action. Review. Lancet Neurology 4, 2005.
  9. Farina, F. Aloisi, E. Meinl. Astrocytes are active players in cerebral innate immunity. Review. Trends in Immunology 28, 2007.
  10. Angela Berzi, C. Korcan Ayata, Paola Cavalcante, Chiara Falcone, Elisabetta Candiago, Teresio Motta, Pia Bernasconi, Reinhard Hohlfeld, Renato Mantegazza, Edgar Meinl, Cinthia Farina. BDNF and its receptors in human myasthenic thymus: Implications for cell fate in thymic pathology. Neuroimmunol. 197, 2008.
  11. Chiara Cordiglieri and Cinthia Farina. Astrocytes exert and control immune responses in the brain. Current Immunology Reviews 6 (3) 2010.
  12. Emanuela Colombo, Stefania Romaggi, Enzo Medico, Ramesh Menon, Flavia Blasevich, Marina Mora, Chiara Falcone, Hanns Lochmüller, Paolo Confalonieri, Renato Mantegazza, Lucia Morandi and Cinthia Farina. The human neurotrophin receptor p75NTR defines differentiation-oriented skeletal muscle precursor cells: implications for muscle regeneration. N.E.N. 70 (2), 2011.
  13. Ramesh Menon and Cinthia Farina. Shared molecular and functional frameworks among five human complex disorders: a comparative study on interactomes linked to susceptibility genes. PLoSONE , 2011.
  14. Emanuela Colombo, Stefania Romaggi, Flavia Blasevich, Marina Mora, Chiara Falcone, Hanns Lochmüller, Lucia Morandi and Cinthia Farina. The neurotrophin receptor p75NTR is induced on mature myofibers in inflammatory myopathies and promotes myotube survival to inflammatory stress. Neuropathol. Applied Neurobiol. Under revision.
  15. Chiara Cordiglieri, Giorgia Melli, Jia Newcombe, Markus Krumbholz, Luis Parada, Enzo Medico, Reinhard Hohlfeld, Edgar Meinl and Cinthia Farina. Astrocytes trigger neurodegeneration through nitric oxide release after TrkB engagement: implications for multiple sclerosis. J. Exp. Med., under revision.