Assistant Professor   
                                                                                         

M.D., 1990, Tohoku University School of Medicine, Sendai, Japan

Major Research Interests: Neurovirology, Viral Pathogenesis, Neuroimmunology, Autoimmunity, Multiple Sclerosis

 

Our research is aimed at elucidating the pathogenesis of autoimmune disorders and virus infections in the central nervous system (CNS), using autoimmune and viral models for multiple sclerosis (MS): experimental autoimmune (allergic) encephalomyelitis (EAE) and Theiler’s murine encephalomyelitis virus (TMEV) infection in mice.  We have studied both host immune responses and pathogens (viruses), in vivo and in vitro, using immunological, virological, and neuropathological methods.  Although axonal degeneration has been described in MS, it was believed to occur only secondarily to demyelination.  We have demonstrated that 1) axonal damage precedes demyelination in TMEV infection (Inside-Out model) and 2) axonal degeneration plays a detrimental role in EAE, while it plays a beneficial role in TMEV infection, and 3) axonal degeneration recruits inflammatory cells to sites of Wallerian degeneration.  We hypothesize that axonal degeneration can be a self-destructive defense mechanism that limits the spread of neurotropic viruses.  We have also conducted studies on the roles of autoreactive CD8+ cytotoxic T cells (CTL) and natural killer T (NKT) cells in TMEV infection and  established a mouse model for primary progressive (PP)- and secondary progressive (SP)-MS.  This established model system will be used to elucidate the roles for cytokines, natural antibody, and apoptosis in lymphoid organs in deciphering how these factors interact and contribute to switching a disease course of autoimmune diseases from relapsing-remitting to a progressive type.

Representative Publications:

Tsunoda I.  (2008).  Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection.  Future Virol. 3 (6): 579-593.   

Tsunoda I, Tanaka T and Fujinami RS.  (2008).  Regulatory role of CD1d in neurotropic virus infection.  J Virol, 82 (20): 10279-10289.

Penberthy WT and Tsunoda I.  (2009).  The importance of NAD in multiple sclerosis.  Curr. Pharm. Des, 15 (1): 64-99.

Tsunoda I, Tanaka T, Taniguchi M and Fujinami RS.  (2009).  Contrasting roles for Va14+ NKT cells in a viral model for multiple sclerosis.  J NeuroVirol, 15 (1): 90-98.

Tsunoda I, Libbey JE and Fujinami RS. (2009).  Theiler's murine encephalomyelitis virus attachment to the gastrointestinal tract is associated with sialic acid binding.  J NeuroVirol, 15 (1): 81-89.

Tsunoda I, Kobayashi-Warren, M, Libbey JE and Fujinami RS.  (2009).  Central nervous system degeneration caused by autoimmune cytotoxic CD8+ T cell clones and hybridomas following virus infection.  Binder MD, Hirokawa N, Windhorst U (eds), Encyclopedia of Neuroscience, Springer-Verlag GmbH Berlin Heidelberg.  pp. 619-625.

Tsunoda I and Fujinami RS.  (2009).  Neuropathogenesis of Theiler’s Murine Encephalomyelitis Virus Infection, a viral model for multiple sclerosis.  J. Neuroimmune Pharmacol,  Epub ahead of print.  

Sato F, Tanaka H, Hasanovic F and Tsunoda I.  (2010).  Theiler’s murine encephalomyelitis virus: Pathophysiology of demyelination and neurodegeneration.  Pathophysiology, in press.

Sato F*, Omura S*, Martinez NE and Tsunoda I.  (2010).  Animal model for multiple sclerosis.  In: Neuroinflammation.  Minagar A (Ed), Elsevier, in press, *Drs Sato and Omura contributed equally.