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) Different form of MS are also being investigated. MS can be divided into four clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP) and progressive relapsing (PR). The pathogenesis of the progressive forms of MS remains unclear, partly due to the lack of animal models that have these clinical patterns of disease.

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

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, Heidelberg, Germany, in press (expected publication date 8-3-08).

Libbey, J.E., and Fujinami, R.S. (2008) Autoimmunity and immunology of autism. In: New Autism Research Developments, BS Mesmere (Ed.), Nova Sciences Publishers, Inc., in press (8-28-07).

Bale, J.F. Jr., and Fujinami, R.S. (2008) Subacute sclerosing panencephalitis. In: Neurotrophic Viral Infections, CS Reiss (Ed.), Cambridge University Press, in press (8-31-07).

Wang, X., Ma, Y., Yoder, A., Crandall, H., Zachary, J., Fujinami, R.S., Weis, J., and Weis, J.J. (2007) T cell infiltration is associated with increased Lyme arthritis in TLR2-/- mice. FEMS Immunology & Medical Microbiology, in press (10-8-07).

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.

Tsunoda, I., Tanaka, T., Saijoh, Y., Doyle, S.E., Terry, E.J., and Fujinami, R.S. (2006) Axonal damage targets inflammatory demyelinating lesions to sites of Wallerian degeneration: Inside-Out model for multiple sclerosis. In: Proceedings of the 8th International Conference of Neuroimmunology (ISNI 2006), T. Tabira, T. Yamamura and J. Kira (Eds.), Medimond, Bologna, Italy, pp. 37-40.

Peterson, L.K., and Fujinami, R.S. (2006) Molecular mimicry. In: Autoantibodies, Second Edition. Y Shoenfeld, ME Gershwin and P-L Meroni (Eds.), Elsevier Press, Philadelphia, pp. 13-20.

Libbey, J.E., Tsunoda, I., and Fujinami, R.S. (2006) Autologous hematopoietic stem cell transplantation: A cure for multiple sclerosis? Future Neurol., 1(4):403-408.

Burgess, N.K., Sweeten, T.L., McMahon, W.M., and Fujinami, R.S. (2006) Hyperserotoninemia and altered immunity in autism. J. Autism Develop. Disorders, 36:697-704.

Fujinami, R.S. (2006) Neurons tame T cells. Nat. Med., 12(5):503-504.

Carlson, N.G., Hill, K.E., Tsunoda, I., Fujinami, R.S., and Rose, J.W. (2006) The pathologic role for COX-2 in apoptotic oligodendrocytes in virus induced demyelinating disease: Implications for multiple sclerosis. J. Neuroimmunol. 174(1-2):21-31.

Libbey, J.E., Peterson, L.K., Tsunoda, I., and Fujinami, R.S. (2006) Monoclonal MOG-reactive autoantibody from progressive EAE has the characteristics of a natural antibody. J. Neuroimmunol., 173(1-2):135-145.

Libbey, J.E.*, Rentz, A.C.*, Fujinami, R.S., Whitby, F.G., and Byington, C.L. (2006) Investigation of treatment failure in neonatal echovirus 7 infection. Ped. Infect. Dis. J. 25(3):259-262, (*equal contribution). [Figures printed online Ped. Infect. Dis. J. 25(3):e5-e6, 2006].

Tsunoda, I., Libbey, J.E., Kobayashi-Warren, M., and Fujinami, R.S. (2006) IFN-g production and astrocyte killing by autoreactive T cells induced by Theiler's virus infection: Role of viral strains and capsid proteins. J. Neuroimmunol., 172(1-2):85-93.

McCoy, L., Tsunoda, I., and Fujinami, R.S. (2006) Multiple sclerosis and virus induced immune responses: Autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity, 39(1):9-19.

Fujinami, R.S., von Herrath, M.G., Christen, U., and Whitton, J.L. (2006) Molecular mimicry, bystander activation or viral persistence: Infections and autoimmune disease. Clin. Microbiol. Rev., 19(1):80-94.

Tsunoda, I., Libbey, J.E., Kuang, L.-Q., Terry, E.J., and Fujinami, R.S. (2005) Massive apoptosis in lymphoid organs in animal models for primary and secondary progressive multiple sclerosis. Am. J. Pathol. 167(6):1631-1646.

Ê Tsunoda, I., Kuang, L.-Q., Kobayashi-Warren, M., and Fujinami, R.S. (2005) Central nervous system pathology caused by autoreactive CD8+ T cell clones following virus infection. J. Virol., 79(23):14640-14646.

Tsunoda, I., and Fujinami, R.S. (2005) TMEV and neuroantigens: Myelin genes and proteins, molecular mimicry, epitope spreading and autoantibody-mediated remyelination. In: Experimental Models of Multiple Sclerosis. E Lavi and CS Constantinescu (Eds.), Springer, New York, pp. 593-616.

Fujinami, R.S. (2005) A tax on luxury: HTLV-1 infection of CD4+CD25+ regulatory T cells. J. Clin. Invest., 115(5):1144-1146.

Libbey, J.E., Sweeten, T.L., McMahon, W.M., and Fujinami, R.S. (2005) Autistic disorder and viral infections. J. NeuroVirol., 11(1):1-10.

Tsunoda, I., Kuang, L-Q., Igenge, I.Z.M., and Fujinami, R.S. (2005) Converting relapsing remitting to secondary progressive experimental allergic encephalomyelitis (EAE) by ultraviolet B irradiation. J. Neuroimmunol., 160(1-2):122-134.

Sweeten, T.L., and Fujinami, R.S. (2004) A potential link between measles virus and autism: age-matched control groups are essential. (Letter to the editor.) Pediat. Neurol., 30(1):78.

Tsunoda, I., Lane, T.E., Blackett, J., and Fujinami, R.S. (2004) Distinct roles for IP-10/CXCL10 in three animal models, Theilers virus infection, EAE, and MHV infection, for multiple sclerosis: implications of differing roles for IP-10 among the subtypes of multiple sclerosis. Multiple Sclerosis, 10(1):26-34.

Von Herrath, M.G., Fujinami, R.S., and Whitton, J.L. (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat. Rev. Microbiol. 1(2):151-157.

Fujinami, R.S., and Sweeten, T.L. (2003) Letting antibodies get to your head. Nat. Med., 9(7):823-825.

Wang, M., Libbey, J.E., Tsunoda, I., and Fujinami, R.S. (2003) Modulation of immune system function by measles virus infection. II. Infection of B cells leads to the production of a soluble factor that arrests uninfected B cells in G0/G1. Viral Immunol., 16(1):45-56.

Libbey, J.E., and Fujinami, R.S. (2003) Viral Demyelinating Disease in Experimental Animals. In: Multiple Sclerosis: Immunology, Pathology, and Pathophysiology. R.M. Herndon (Ed.), Demos Medical Publishing, Inc., New York, pp. 125-133.

Tsunoda, I., Kuang, L.-Q., Libbey, J.E., and Fujinami, R.S. (2003) Axonal Injury Heralds Virus Induced Demyelination. Am. J. Pathol., 162(4):1259-1269.

Wang, M., Howell, J., Libbey, J.E., Tainer, J.A., and Fujinami, R.S. (2003) Manganese Superoxide Dismutase Induction during Measles Virus Infection. J. Med. Virol., 70(3):470-474.

Tsunoda, I. and Fujinami, R.S. (2002) Inside-Out versus Outside-In Models for Virus Induced Demeylination: Axonal Damage Triggering Demyelination. Springer Semin. Immunopathol., 24(2):105-125.

Tsunoda, I., Kuang, L.-Q., and Fujinami, R.S. (2002) Induction of Autoreactive CD8+ Cytotoxic T Cells during TheilerÕs Murine Encephalomyelitis Virus Infection: Implications for Autoimmunity. J. Virol., 76(24):12834-12844.

Libbey, J.E., Tsunoda, I., and Fujinami, R.S. (2002) Altered Cell Growth and Morphology in a BHK-21 Cell Mutant that Lacks a Receptor for Theiler's Murine Encephalomyelitis Virus (TMEV). Virology, 294(1):85-93.

McCright, I.J., Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (2002) Mutation in Loop I of VP1 of Theiler's Virus Delays Viral RNA Release into Cells and Enhances Antibody-Mediated Neutralization: A Mechanism for the Failure of Persistence by the Mutant Virus. J. NeuroVirol., 8(2):100-110.

Libbey, J.E., and Fujinami, R.S. (2002) Virus Induced Immunosuppression. In: Polymicrobial Diseases, K.A. Brogden and J.M. Guthmiller (Eds.), ASM Press, Washington, D.C., pp. 377-87.

Libbey, J.E., and Fujinami, R.S. (2002) Are Virus Infections as Triggers for Autoimmune Disease? Clinical Microbiology Newsletter, 24:73-76.

Fujinami, R.S. (2002) Molecular Mimicry that Primes for Autoimmunity which is Triggered by Infection. Molecular Psychiatry, 7 Suppl 2:S32-33.

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