ROBERT S. FUJINAMI
Robert Fujinami
e-mail: Robert.Fujinami@hsc.utah.edu		 Professor of Pathology

Neurobiology of Disease
Brain and Behavior

B.A. 1972, University of Utah; Ph.D. 1977, Northwestern University.

RESEARCH:

The laboratory of Dr. Fujinami focuses on various concepts of viral pathogenesis and autoimmunity. To address questions concerning pathogenesis and autoimmunity, four model systems are utilized.

1) Theiler's murine encephalomyelitis virus (TMEV) infection of mice is a relevant animal model for the human demyelinating disease multiple sclerosis (MS). TMEV belongs to the Picornaviridae family and are in the Cardiovirus genus. These viruses are small positive-sense single-stranded RNA viruses. Infection of mice with the DA strain of TMEV causes an acute polioencephalomyelitis where mice survive and later develop a central nervous system (CNS) inflammatory demyelinating disease. This mirrors the progressive forms of MS.

2) The lab also is investigating why no one agent is responsible for exacerbations of multiple sclerosis. Numerous reports indicate the important role infections may play in multiple sclerosis (MS) and other autoimmune diseases. There are reports associating attacks and/or exacerbations of MS with viral infections. These infections are thought to be involved in the disease by expanding autoreactive T cells in genetically susceptible individuals. More than a dozen viruses have been isolated from MS in the past 50 years, but no single virus has been singled out as the "MS virus."

3) We have created a new infectious agent model for temporal lobe epilepsy. In our previous studies SJL/J mice infected with TMEV develop a persistent viral infection with an inflammatory demyelinating pathology in the CNS. In recent studies, C57BL/6 mice infected with TMEV develop acute seizures that resolve and later have spontaneous seizures. TMEV in C57BL/6 mice targets the hippocampus. The ensuing acute innate inflammatory response contributes to the acute seizures. We are investigating the contributions of the innate immune response to the acquisition of seizures.

4) The last project investigates the etiology and pathogenesis of autism. This developmental disease is acknowledged as a syndrome having a broad range of symptoms. It appears that genetics play a major role in the development of this disease and environmental factors may also be involved. We are investigating the potential role of virus infections and autoimmune responses to CNS proteins in individuals.

Selected Publications

Libbey, J.E., and Fujinami, R.S. (2009) Potential triggers of MS. In: Molecular Basis of Multiple Sclerosis. The Immune System. Series: Results and Problems in Cell Differentiation. R Martin, A Lutterotti (Eds.), Springer-Verlag, Berlin, epub January 8, 2009.

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

Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (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, J.E., and Fujinami, R.S. (2008) Central nervous system degeneration caused by autoimmune cytotoxic CD8+ T cell clones and hybridomas following virus infection. In: Encyclopedia of Neuroscience: Neuroimmunology. MD Binder, N Hirokawa, U Windhorst, MC Hirsch (Eds.), Springer, New York, pp. 619-625.

Bale, J.F. Jr., and Fujinami, R.S. (2008) Subacute sclerosing panencephalitis. In: Neurotrophic Viral Infections, CS Reiss (Ed.), Cambridge University Press, pp. 26-34.

Theil, D.J., Libbey, J.E., Rodriguez, F., Whitton, J.L., Tsunoda, I., Derfuss, T.J., and Fujinami, R.S. (2008) Targeting myelin proteolipid protein to the MHC class I pathway by ubiquitination modulates the course of experimental allergic encephalomyelitis. J Neuroimmunol, 204:92-100.

Peterson, L.K., Masaki, T., Wheelwright, S.R., Tsunoda, I., and Fujinami, R.S. (2008) Cross-reactive myelin antibody induces renal pathology. Autoimmunity, 41(7):526-536.

Tsunoda, I., Tanaka, T., and Fujinami, R.S. (2008) Regulatory role of CD1d in neurotropic virus infection. J Virol, 82(20):10279-89.

Peterson, L.K., Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (2008) Role of B:T cell ratio in suppression of clinical signs: A model for silent MS. Exp Mol Path, 85(1):28-39.

Peterson, L.K., Tsunoda, I., and Fujinami, R.S. (2008) Role of CD5+ B-1 cells in EAE pathogenesis. Autoimmunity, 41(5):353-362.

Libbey, J.E., Kirkman, N.J., Smith, M.C.P., Tanaka, T., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2008) Seizures following picornavirus infection. Epilepsia, 49(6):1066-1074.

Fujinami, R.S., and Oldstone, M.B.A. (2008) Immunopathology of virus infection. In: Encyclopedia of Virology, Third Edition, B Mahy, MHV van Regenmortel (Eds.), Elsevier, Oxford, UK, (Vol. 3 of 5 Vol. set) pp. 78-83.

Libbey, J.E., Coon, H.H., Kirkman, N.J., Sweeten, T.L., Miller, J.N., Stevenson, E.K., Lainhart, J.E., McMahon, W.M., and Fujinami, R.S. (2008) Are there enhanced MBP autoantibodies in autism? J Autism Dev Disord, 38:324-332.

Kirkman, N.J.*, Libbey, J.E.*, Sweeten, T.L., Coon, H.H., Miller, J.N., Stevenson, E.K., Lainhart, J.E., McMahon, W.M., and Fujinami, R.S. (2008) How relevant are GFAP autoantibodies in autism and Tourette syndrome? J Autism Dev Disord, 38:333-34 (*equal contribution).

Wang, X., Ma, Y., Yoder, A., Crandall, H., Zachary, J., Fujinami, R.S., Weis, J., and Weis, J.J. (2008) T cell infiltration is associated with increased Lyme arthritis in TLR2-/- mice. FEMS Immunology & Medical Microbiology, 52:124:133.

Tsunoda, I., Tanaka, T., Saijoh, Y., and Fujinami, R.S. (2007) Targeting inflammatory demyelinating lesions to sites of Wallerian degeneration. Am. J. Pathol., 171(5):1563-1575.

Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (2007) TGF-B1 suppresses T cell infiltration and VP2 Puff B mutation enhances apoptosis in acute polioencephalitis induced by Theiler's virus. J. Neuroimmunol., 190(1-2):80-89.

Tsunoda, I., and Fujinami, R.S. (2007) Neuropathogenesis of Theiler's murine encephalomyelitis virus infection. In: Encyclopedia of Bioscience, "RNA viruses and CNS diseases: Mechanisms pathogenesis and persistence," X. Zhang (Ed.), Frontiers in Bioscience, http://www.bioscience.org, in press.

Fujinami, R.S., and Oldstone, M.B.A. (2007) Immunopathology of virus infection. In: Encyclopedia of Virology, 3rd Edition, B Mahy and M van Regenmortel (Eds.), Elsevier, Oxford, UK, in press.

Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (2007) Sequential polymicrobial infections lead to CNS inflammatory disease: Possible involvement of bystander activation in heterologous immunity. J. Neuroimmunol., 188(1-2) 22-33.

Libbey, J.E., Coon, H.H., Kirkman, N.J., Sweeten, T.L., Miller, J.N., Stevenson, E.K., Lainhart, J.E., McMahon, W.M., and Fujinami, R.S. (2007) Are there enhanced MBP autoantibodies in autism? J. Autism Dev. Disord., epub ahead of print, June 22, 2007.

Kirkman, N.J.*, Libbey, J.E.*, Sweeten, T.L., Coon, H.H., Miller, J.N., Stevenson, E.K., Lainhart, J.E., McMahon, W.M., and Fujinami, R.S. (2007) How relevant are GFAP autoantibodies in autism and Tourette syndrome? J. Autism Dev. Disord., epub ahead of print, June 20, 2007. (*equal contribution)

Libbey, J.E., Coon, H.H., Kirkman, N.J., Sweeten, T.L., Miller, J.N., Lainhart, J.E., McMahon, W.M., and Fujinami, R.S. (2007) Are there altered antibody responses to measles, mumps or rubella viruses in autism? J. NeuroVirol., 13:252-259.

Welsh, R.M., and Fujinami, R.S. (2007) Pathogenic epitopes, heterologous immunity, and vaccine design. Nat. Rev. Microbiol., 5(7):555-563.

Libbey, J.E., McCoy, L.L., and Fujinami, R.S. (2007) Molecular mimicry in multiple sclerosis. Int. Rev. Neurobiol., 79C:127-147.

Peterson, L.K., and Fujinami, R.S. (2007) Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of multiple sclerosis. J. Neuroimmunol. (Special Issue on Neurodegeneration), 184(1-2):37-44.

Tsunoda, I., Terry, E.J., Marble, B.J., Lazarides, E., Woods, C., and Fujinami, R.S. (2007) Modulation of experimental allergic encephalomyelitis by VLA-2 blockade. Brain Pathol., 17(1):45-55.

Libbey, J.E., Tsunoda, I., Whitton, J.L., and Fujinami, R.S. (2007) Infectious RNA isolated from the spinal cords of mice chronically infected with Theiler's murine encephalomyelitis virus. J. Virol., 81(6):3009-3011.

Peterson, L.K., Tsunoda, I., Masaki, T., and Fujinami, R.S. (2007) Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for systemic autoimmunity in progressive experimental autoimmune encephalomyelitis. J. Neuroimmunol., 183(1-2):69-80.

Tsunoda, I., Tanaka, T., Terry, E.J., and Fujinami, R.S. (2007) Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial? Am. J. Pathol., 170(1):214-226.

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