Robert S. Fujinami, Ph.D.

Robert S. Fujinami, Ph.D.

Professor of Pathology

Adjunct Professor of Neurology

Lab Webpage

robert.fujinami@hsc.utah.edu

Phone: 801-585-3305

3R330 SOM School of Medicine

Faculty Assistant:   Kathleen Borick  

 
Scholarly Emphasis: Neurovirology, Neuroimmunology

We have several on-going projects in the lab.  The first project involves an experimental animal model for the human demyelinating disease multiple sclerosis (MS).  MS has been proposed to be initiated by environmental triggers such as virus infections in genetically susceptible individuals.  We use Theiler’s murine encephalomyelitis virus (TMEV) infection of SJL/J mice to test this hypothesis.  TMEV belongs to the Picornaviridae family and is in the Cardiovirus genus and Theilovirus species.  Recently it was discovered that the general population is infected with a human Theilovirus.  Infection of SJL/J mice with the DA strain of TMEV leads to a persistent infection where mice develop a chronic inflammatory demyelinating disease.  The adaptive immune response to the persistent virus infection results in the demyelinating disease.  CD8+ and CD4+ T cells as well as antibodies are involved in the pathogenesis of TMEV induced demyelinating disease.  CD8+ T cells are to be responsible for viral clearance in and protection from the demyelinating disease in resistant strains of mice.  CD4+ T cells are involved in the inflammatory CNS demyelinating disease.  CD8+ T cells have also been shown to influence demyelination in DA virus infected mice as well as CD8+ T cells outnumber CD4+ T cells in MS lesions in brain tissue.  We have been exploring how dual reactive CD8+ T cells induced by DA virus infection are involved in the demyelinating disease.  We are testing two hypotheses.  The first is that there is molecular mimicry between DA virus and self proteins.  As part of this hypothesis is that infection with DA virus results in anti-viral CD8+ T cells that recognize both virus and myelin epitopes.  These CD8+ T cells are expanded following DA virus infection, go into the central nervous system (CNS) where the virus and myelin antigens are present and initiate demyelinating disease.  The second hypothesis to be tested is that the anti-viral CD8+ T cells have multiple T cell receptors (TCRs).  Combination of the Vα and Vβ change could recognize virus and myelin epitopes presented in the context of class I MHC molecules.  Such CD8+ T cells recognizing myelin antigens in the CNS could then result in demyelinating disease.  These studies could help in our understanding how virus infections can trigger autoimmune disease.

The second project is investigating a new animal model for epilepsy.  Infection of C57BL/6 mice with the TMEV results in acute encephalitis.  This inflammation of the brain due to virus infection causes acute seizures.  The acute seizures occur between day 3 and 10 post infection.  In contrast to SJL/J mice, C57BL/6 mice clear the virus by about 2 month post infection and around this time mice start developing spontaneous seizures/epilepsy.  DA virus infection targets the hippocampus, particularly CA1.  We are currently investigating the role of the innate immune response to DA virus infection that causes the acute seizures.  The virus and innate immune response to the virus causes cell death of hippocampal neurons.  This region is involved in the acute seizures.  In addition, we have evidence that TNF-α, IL-6 and complement all play a role in the development of the acute seizures.  We are exploring what cells in the CNS of infiltrating immune cells are responsible for producing different cytokines and complement components involved in the elaboration of acute seizures.  These studies will help develop new treatments and/or therapies for epilepsy.

A third project is in collaboration with Dr. Nikolaus Trede.  The goal of this project is to identify new compounds that can be used to treat MS.  We use an animal model for MS known as experimental autoimmune encephalomyelitis (EAE).  In SJL/J mice we can induce a relapsing-remitting disease similar to relapsing-remitting MS.  Dr. Trede is using a zebrafish screen to identify compound(s) that alter T cells.  One of these compounds when given to mice can stop attacks (relapses) of clinical disease as well as significantly reduce the demyelination and inflammation present in the CNS of treated mice.  We are investigating how this compound works and its efficacy in this animal model for MS.  We have evidence that T cells are targeted by the compound markedly suppressed.  These studies will aid in new therapies and treatments for MS.

Selected Publications

  • (Out of total of 192 publications)
  • 1. Tsunoda I, Libbey JE, Fujinami RS. Theiler’s murine encephalomyelitis virus attachment to the gastrointestinal tract is associated with sialic acid binding. J NeuroVirol 15(1):81-9, 2009. PMID: 19115131; PMCID: PMC2882804
  • 2. Tsunoda I, Tanaka T, Taniguchi M, Fujinami RS. Contrasting roles for Valpha14+ NKT cells in a viral model for multiple sclerosis. J NeuroVirol 15(1):90-8, 2009. PMID: 19115130; PMCID: PMC2671644
  • 3. Kirkman NJ*, Libbey JE*, Wilcox KS, White HS, Fujinami RS. Innate but not adaptive immune responses contribute to behavioral seizures following viral infection. Epilepsia 51(3)454-64, 2010. * equal contribution PMID: 19845729; PMCID: PMC3046460 Cover art.
  • 4. Libbey JE, Tsunoda I, Fujinami RS. Studies in the modulation of experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol 5(2):168-175, 2010. PMID: 20401539; PMCID: PMC3046865
  • 5. Libbey JE, Kirkman NJ, Wilcox KS, White HS, Fujinami RS. Role for complement in the development of seizures following acute viral infection. J Virol 84(13):6452-60, 2010. PMID: 20427530; PMCID: PMC2903264 [JVI Spotlight, Brain complement activation during viral encephalitis. J Virol 84(13):6268, 2010.]
  • 6. Libbey JE, Fujinami RS. Role for antibodies in altering behavior and movement. Autism Res 3:1-6, 2010. PMID: 20589715
  • 7. Tsunoda I, Fujinami RS. Neuropathogenesis of Theiler’s murine encephalomyelitis virus infection, an animal model for multiple sclerosis. J Neuroimmune Pharmacol 5(3):355-69, 2010. PMID: 19894121; PMCID: PMC2888670
  • 8. Libbey JE, Fujinami RS. Potential triggers of MS. [In: R Martin and A Lutterotti (Eds.), Molecular Basis of Multiple Sclerosis. The Immune System, Springer, New York, Berlin & Heidelberg, 2009] Results Probl Cell Differ 51:21-42, 2010. PMID: 19130026 PMCID: PMC3048788
  • 9. Stewart K-AA, Wilcox KS, Fujinami RS, White HS. Theiler’s virus infection chronically alters seizure susceptibility. Epilepsia 51(8):1418-28, 2010. PMID: 20002148; NIHMSID# 259793
  • 10. Kemball C, Fujinami RS, Whitton JL. Adaptive immune responses. In The Picornaviruses E Erhenfeld, E Domingo, R Roos (Eds.), ASM Press, Washington, D.C., 2010, pp. 303-19.
  • 11. Stewart KA-A, Wilcox KS, Fujinami RS, White HS. Development of postinfection epilepsy following Theiler’s virus infection of C57BL/6 mice. J Neuropathol Exp Neurol, 69(12):1210-9, 2010. PMID: 21107134; PMCID: PMC3077028
  • 12. Libbey JE, Fujinami RS. Experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines. Vaccine 29(17):3356-3362, 2011. PMID: 20850537; PMCID: PMC3017664
  • 13. Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Interleukin-6, produced by resident cells of the central nervous system and infiltrating cells, contributes to the development of seizures following viral infection. J Virol 85(14):6913-6922, 2011. PMID: 21543484
  • 14. Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Lack of correlation with central nervous system inflammation and neuropathology in the development of seizures following acute virus infection. J Virol 85(16):8149-8157, 2011. PMID: 21680509
  • 15. Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Once initiated, viral encephalitis-induced seizures are consistent no matter the treatment or lack of interleukin-6. J NeuroVirol 17(5):496-99, 2011
  • 16. Libbey JE, Fujinami RS. Adaptive immune response to viral infections in the central nervous system. Handbook of Clinical Neurology, invited contribution, in press(5-19-2011).
  • All Publications: Click Here

Honors and Awards

  • 1968, Japanese American Citizens League Scholarship, Salt Lake City, Utah Chapter
  • 1968, University of Utah Presidential Scholarship
  • 1981-1983, National Institutes of Health, New Investigator Award
  • 1982-1986, National Multiple Sclerosis Society Harry M. Weaver Neuroscience Scholar, National Multiple Sclerosis Society (Career Development Award)
  • 1988, Nobel Medica Research Forum, Honorary Lecturer
  • 1989-1996, National Institutes of Health, Javits Neuroscience Scholar Award

Professional Education

  • 1968-1972, B.A., University of Utah, Salt Lake City, Utah (Microbiology)
  • 1972-1977, Ph.D., Northwestern University, Chicago, Illinois (Immunology/Microbiology)
  • 1977-1980, Postdoctoral, The Scripps Research Institute [formerly Scripps Clinic and Research Foundation], LaJolla, California (Immunology)