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:

Neuroimmunology/Neurovirology - Understanding immune and viral contributions to the pathogenesis of multiple sclerosis and epilepsy

Virus infection leading to central nervous system (CNS) demyelination.
Theiler's virus causes an encephalomyelitis in mice and this infection mimics multiple sclerosis (MS) in humans. The virus spreads through the CNS and infects white matter particularly the oligodendrocytes and astrocytes. This project involves understanding the virologic and immunologic participation in this CNS demyelinating disease.

How virus infection modulates immune responses leading to autoimmune disease.
Genetically altered viruses encoding myelin proteins can either protect against or enhance an autoimmune disease known as experimental allergic encephalomyelitis (EAE). This is a model for the human disease, MS. These data were generated using viruses encoding myelin basic protein, and myelin proteolipid protein. Other viral constructs coding for other CNS proteins need to be characterized. This project involves definition of how these viral constructs can modulate immune responses and whether infection leads to autoimmune disease.

Virus Infection and Epilepsy.
We have created a new infectious agent model for temporal lobe epilepsy. In our previous studies, SJL/J mice infected with Theiler's murine encephalomyelitis virus (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.


Selected Publications:

Libbey, J.E., and Fujinami, R.S. (2016) Variable Genome Sequences of the Murine Pneumotropic Virus (Polyomaviridae) Regulatory Region Isolated from an Infected Mouse Tissue Viral Suspension. Genome Announc., 4(3):e00405-e00416. PMID: 27231357

Libbey, J.E., and Fujinami, R.S. (2016) Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1). Genome Announc., 4(3):e00404-e00416. PMID: 27198030

Libbey, J.E., Doty, D.J., Sim, J.T., Cusick, M.F., Round, J.L., and Fujinami, R.S. (2016) The effects of diet on the severity of central nervous system disease: one part of lab-to-lab variability. Nutrition, 32:877-883. PMID: 27133811

Libbey, J.E., Hanak, T.J., Doty, D.J., Wilcox, K.S., and Fujinami, R.S. (2016) NBQX, a Highly Selective Competitive Antagonist of AMPA and KA Ionotropic Glutamate Receptors, Increases Seizures and Mortality Following Picornavirus Infection. Exp. Neurol., 280:89-96. PMCID: PMC4860063

Vezzani, A., Fujinami, R.S., White, H.S., Preux, P.M., Blumcke, I., Sander, J.W., and Loscher, W. (2016) Infections, Inflammation and Epilepsy. Acta Neuropathol, 131(2):211-234. PMCID: PMC4867498

Smeal, R.M., Fujinami, R.S., White, H.S., and Wilcox, K.S. Decrease in CA3 inhibitory network activity during Theiler's virus encephalitis. Neurosci Lett, 609:210-215. PMID: 26477780

Cusick, M.F., Libbey, J.E., Oh, L., Jordan, S., and Fujinami, R.S. (2015) Acthar Gel Treatment Suppresses Acute Exacerbations in a Murine Model of Relapsing-Remitting Multiple Sclerosis. Autoimmunity, 48(4):222-230. PMCID: PMC4439322

Williams, M.A., and Fujinami, R.S. (2014) Immunopathology, Reference Module in Biomedical Sciences. Elsevier. October 27, 2014.

Cusick, M.F., Libbey, J.E., Doty, D.J., and Fujinami, R.S. (2014) DA Virus Mutant H101 has Altered CNS Pathogenesis and Causes Immunosuppression. J. Neuroimmunol., 277(1-2):118-126.

Libbey, J.E., Lane, T.E., and Fujinami, R.S. (2014) Axonal pathology and demyelination in viral models of neurology disease. Discovery Med., 18(97):79-89. PMID: 25091490

Libbey, J.E., and Fujinami, R.S. (214) Adaptive immune response to viral infections in the central nervous system. [In Neurovirology. A Tselis and J Boss (Eds), Elsevier, San Diego] The Handbook of Clinical Neurology 123:225-247, August 31, 2014. PMID: 25015488

Libbey, J.E., Cusick, M.F., and Fujinami, R.S. (2014) Role of Pathogens in Multiple Sclerosis. Int. Rev. Immunol., 33(4):266-283. PMID: 24266364 (NIH T32AI055434 and NIH 1R01NS082102)

Cusick, M.F., Libbey, J.E., and Fujinami, R.S. (2014) Picornavirus Infection Leading to Immunosuppression. Fut Virol, 9(5):475-482. (NIH T32AI055434 and NIH 1R01NS082102, and Emma Mary DeLand Foundation)

Wang, X., Cusick, M.F., Wang, Y., Sun, P., Libbey, J.E., Fujinami, R.S., and Song, S.-K. (2014) Diffusion basis spectrum imaging detects and distinguishes coexisting subclinical inflammation, demyelination, and axonal injury in experimental autoimmune encephalomyelitis mice. NMR in Biomedicine, 27:843-852. PMCID: PMC4071074 (NIH T32AI055434, NIH 1R01NS082102, and Emma Mary DeLand Foundation)

Cusick, M.F., Libbey, J.E., Trede, N.S., and Fujinami, R.S. (2014) Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease. PLoS ONE, 9(4):e94486. PMCID: PMC3981810 (NIH T32AI055434 and Emma Mary DeLand Foundation)

Fujinami, R.S. (2014) Reviews in neuroimmunology. J NeuroVirol, 20(2):105-106. PMID: 24549969

Cusick, M.F., Libbey, J.E., Gill, J.C., Fujinami, R.S., and Eckels, D.D. (2013) CD4+ T-Cell Engagement by Both Wild-Type and Variant HCV Peptides Modulates the Conversion of Viral Clearing Helper T Cells to Tregs. Fut Virol, 8(7):695-705, 2013. PMCID: PMC3887522 (NIH T32AI055434 and Emma Mary DeLand Foundation)

Cusick, M.F., Libbey, J.E., and Fujinami, R.S. (2013) Multiple Sclerosis: Autoimmunity and Viruses. Curr. Opin. Rheumatol, 25(4):496-501. PMID: 23656710 (NIH 5R01NS065714-03, NIH T32AI055434, and Emma Mary DeLand Foundation)

Trede, N.S., Heaton, W., Ridges, S., Hossein, S., Cusick, M., Bearss, D., Jones, D., and Fujinami, R.S. (2013) Discovery of Biologically Active Oncologic and Immunologic Small Molecule Therapies using Zebrafish: Overview and Example of Modulation of T cell Activation. Curr. Protoc. Pharmacol, Chapter 14:14.24, 2013. PMID: 23456612

Loughran, G., Libbey, J.E., Uddowla, S., Scallan, M.F., Ryan, M.D., Fujinami, R.S., Rieder, E., and Atkins, J.F. (2013) Theiler's Murine Encephalomyelitis Virus Contrasts with Encephalomyocarditis and Foot-and-Mouth Disease Viruses in its Functional Utilization of the StopGo Non-standard Translation Mechanism. J. Gen. Virol, 94:348-353. PMCID: PMC3709618 (NIH 1R01NS065714)

Cusick, M.F., Libbey, J.E., Patel, D.C., Doty, D.J., and Fujinami, R.S. (2013) Infiltrating macrophages are key to the development of seizures following virus infection. J Virol, 87(3):1849-1860. PMCID: PMC3554195 [The Scientist Editor's Choice in Immunology, Viruses on the Brain. May 1, 27(5), 2013.] (Emma Mary DeLand Foundation, NIH 5R01NS065714-03, and NIH T32AI055434)

Libbey, J.E., Tsunoda, I., and Fujinami, R.S. (2012) Possible Role of IL-17 in a prime/challenge model of multiple sclerosis. J NeuroVirol, 18(6):471-478. PMCID: PMC3508306 (NIH R01AI058105-05)

Cusick, M.F., Libbey, J.E., Fujinami, R.S., and Eckels, D.D. (2012) In Vitro Antigen-Specific Induction of IL-22 in Human Subjects that Resolved HCV Infection. Fut Virol, 7(7):719-728. PMCID: PMC3505095 (Emma Mary DeLand Foundation and NIH 5R01AI047347-11)

Tsunoda, I., Libbey, J.E., and Fujinami, R.S. (2012) Immunization with structural and non-structural proteins of Theiler's murine encephalomyelitis virus alters demyelinating disease. J NeuroVirol, 18(2):127-137. PMCID: PMC3335973 (NIH-5R01NS34497-04)

Smeal, R.M., Stewart, K.A., Iacob, E., Fujinami, R.S., White, H.S., and Wilcox, K.S. (2012) The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy. J NeuroVirol, 18(1):30-44. PMID 22328242 (NIH-1R01NS065714)

Libbey, J.E., Cusick, M.F., Tsunoda, I., and Fujinami, R.S. (2012) Antiviral CD8+ T cells cause an experimental autoimmune encephalomyelitis-like disease in naïve mice. J NeuroVirol, 18(1):45-54. PMCID: PMC3327473 (NIH-5R01NS34497 and Emma Mary DeLand Foundation)

Cusick, M.F., Libbey, J.E., Trede, N.K., Eckels, D.D., and Fujinami, R.S. (2012) Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen. J Neuroimmunol, 244(1-2):35-44. PMID: 22245285 (Emma Mary DeLand Foundation)

Cusick, M.F., Libbey, J.E., and Fujinami, R.S. (2012) Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allerg Immunol (special issue on Hypotheses of Autoimmune Diseases), 42(1):102-11. PMCID: PMC3266166 (NIH-R01NS065714-02)

Libbey, J.E., and Fujinami, R.S. (2011) Neurotropic viral infections leading to epilepsy: focus on Theiler's murine encephalomyelitis virus. Fut Virol, 6(11):1339-1350. PMCID: PMC3259611 (NIH-R01NS065714)

Libbey, J.E., Kennett, N.J., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2011) Once initiated, viral encephalitis-induced seizures are consistent no matter the treatment or lack of interleukin-6. J NeuroVirol, 17(5):496-99. PMCID: PMC3250218 (NIH-R01NS065714-01A1/02)

Libbey, J.E., Kennett, N.J., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2011) Lack of correlation with CNS inflammation and neuropathology in the development of seizures following acute virus infection. J Virol, 85(16):8149-8157. PMCID: PMC3147986 (Margolis Foundation, Citizens United for Research in Epilepsy, Emma Mary DeLand Foundation and NIH-NS065714)

Libbey, J.E., Kennett, N.J., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2011) 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. PMCID: PMC3126579 (Margolis Foundation, Citizens United for Research in Epilepsy, Emma Mary DeLand Foundation and NIH-NS065714)

Libbey, J.E., and Fujinami, R.S. (2011) Experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines. Vaccine, 29(17):3356-3362. PMCID: PMC3017664 (NIH-AI58105)

Stewart, KA.-A., Wilcox, K.S., Fujinami, R.S., and White, H.S. (2010) Development of postinfection epilepsy following Theiler's virus infection of C57BL/6 mice. J Neuropathol Exp Neurol, 69(12):1210-1219. PMCID: PMC3077028 (NIH-NS065714)

Kemball, C., Fujinami, R.S., and Whitton, J.L. (2010) Adaptive immune responses. In: The Picornaviruses, E. Erhenfeld, E. Domingo, R, Roos (Eds.), ASM Press, Washington, D.C., 303-319. (NIH-NS065714 and NIH-AI058105)

Stewart, K-A.A., Wilcox, K.S., Fujinami, R.S., and White, H.S. (2010) Theiler's virus infection chronically alters seizure susceptibility. Epilepsia 51(8):1418-1428. (Citizens United for Research in Epilepsy and Margolis Foundation)

Libbey, J.E., and Fujinami, R.S. (2010) 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. PMCID: PMC3048788 (NIH-AI58105)

Tsunoda, I., and Fujinami, R.S. (2010) Neuropathogenesis of Theiler's murine encephalomyelitis virus infection, an animal model for multiple sclerosis. J Neuroimmune Pharmacol, 5(3):355-369. PMCID: PMC2888670 (NIH-AI58105)

Libbey, J.E., and Fujinami, R.S. (2010) Role for antibodies in altering behavior and movement. Autism Res, 3:1-6. (Autism Speaks 2728 and Emma Mary DeLand Foundation)

Libbey, J.E., Kirkman, N.J., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2010) Role for complement in the development of seizures following acute viral infection. J Virol, 84(13):6452-6460. [JVI Spotlight Brain complement activation during viral encephalitis. J Virol 84(13):6268, 2010.] (Margolis Foundation, Citizens United for Research in Epilepsy, Emma Mary DeLand Foundation and NIH-NS065714)

Libbey, J.E., Tsunoda, I., and Fujinami, R.S. (2010) Studies in the modulation of experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol, 5(2):168-175. PMCID: PMC3046865 (NIH-AI058105)

Kirkman, N.J.*, Libbey, J.E.*, Wilcox, K.S., White, H.S., and Fujinami, R.S. (2010) Innate but not adaptive immune responses contribute to behavioral seizures following viral infection. Epilepsia, 51(3)454-464. * equal contribution PMCID: PMC3046460 Cover art. (Margolis Foundation, Citizens United for Research in Epilepsy, Emma Mary DeLand Foundation and NIH-NS065714)