Neuroimmunology

Professor Claude Bernard DES (Sorbonne), Msc (Montr), DSc (Stras)

Group Leader

Telephone:
+61 - 3 9905 0623 (Office)

Facsimile:
+61 - 3 9905 0680

Email:
claude.bernard@med.monash.edu.au

Contact

Postal:
Monash Immunology and Stem Cell Laboratories (MISCL)
STRIP1, Level 3
Monash University
Clayton 3800

Lab Members

Research Fellows

Dr Michael Azari, BAppSc (Chiro), PhD
Dr Phil Heraud, PhD
Daniella Herszfeld, MSc
Dr Sara Litwak, PhD
Dr Krishnakumar Menon, PhD
Dr Leon Moussa
Dr Steven Petratos, PhD
Dr Chris Siatskas, PhD
Dr Guizhi Sun, MD
Dr Shunhe Wang, MD, PhD

Research assistants

Naomi Campanale, MSc
Ashley Emerson-Webber, BSc Hons.

Postgraduate students

Sally Caine, BSc Hons.
Courtney McDonald, BSc Hons.
Ezgi Ozturk, BSc Hons.
Natalie Payne, BSc Hons.
Dr Martin Short. MBBS, FRACP

Honours students

No honours students for 2009

Research interests

The major focus of the Neuroimmunology Laboratory is to study in human and experimental animals, facets of immunology, genetics, biochemistry, microbiology and behaviour pertaining to the causation of various acute, progressive and destructive neurological disorders such as Multiple Sclerosis (MS). The major objective of our research is to understand the basic underpinnings of MS and attempt to translate these findings to develop new therapeutic strategies for people with MS.

Multiple Sclerosis Research Group (pdf, 102kb)

Specifically we are interested in

• Development of therapeutics to a) suppress the auto-inflammatory response and b) to promote and enhance CNS regeneration.
• Understanding factors contributing to susceptibility and the molecular and cellular mechanisms underlying the disease process.
• Recently, we have discovered that targeting Nogo-A, a specific molecule responsible for preventing neurite outgrowth and consequently the failure of the central nervous system to regenerate, blunts clinical signs and pathology associated with the EAE model of MS. This suggests that blockade of this deleterious molecule may help maintain and/or restore the neuronal integrity of the CNS following immune insult in diseases like MS.

Selected Publications

Barnard, A., D. Layton, M. Hince, S. Sakkal, C. Bernard, A. Chidgey, and R. Boyd, Impact of the neuroendocrine system on thymus and bone marrow function. Neuroimmunomodulation, 2008. 15: 7-18.

Barnard, A.L., A.P. Chidgey, C.C. Bernard, and R.L. Boyd, Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis. Blood, 2008. E-Pub.

Chan, J., E.J. Ban, K.H. Chun, S. Wang, J. McQualter, C. Bernard, B.H. Toh, and F. Alderuccio, Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Autoimmunity, 2008. 41: 405-13.

Siatskas C and Bernard CCA (2008) Stem cell and gene therapeutic strategies for the treatment of multiple sclerosis. Current Molecular Medicine. (Invited Review).

Azari MF, Ozturk E, Profyris C, Wang S, Small DH, Bernard CC, Petratos S. (2008) LIF-treatment reduces Nogo-A deposits in spinal cord injury modulating Rho GTPase activity and CRMP-2 phosphorylation. Journal of Neurodegeneration and Regeneration

Azari, M., Ozturk, E., Profyris, C., Wang, S., Small, D., Bernard, C.C.A. and Petratos, S. Leukemia Inhibitory Factor Arrests Oligodendrocyte Death and Demyelination in Spinal Cord Injury. Journal of Neurodegeneration and regeneration, 2008; 65: 914-929.

Chan, J., Ban, E.J., Chun, K.H., Wang, S., McQualter, J., Bernard, C.C.A., Toh, B.H. and Alderuccio, F. Autoimmunity. (2008) (In press, accepted May 2008).

Petratos S., Li QX., George AJ., Kerr ML., Unabia SE., Hatzinisiriou I., Maksel D., Aguilar MI., Small DH. (2008) The beta-amyloid protein of Alzheimer’s disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism. Brain 131, 90-108

Small, D.H. Petratos, S., Unabia, S. and Maksel, D. (2008) Expression of acetylcholinesterase in Alzheimer's disease brain. Role in neuritic dystrophy and synaptic scaling. In Advances in Alzheimer's disease and Parkinson's disease. Insights, Progress, and Perspectives Spinger US Vol 57 p429-437.

Payne, N., Siatskas, C. and Bernard, C. C. (2008) The promise of stem cells and regenerative therapies for multiple sclerosis. J. Autoimmun. In press.

Otaegui O, Mostafavi S, Bernard CCA, Lopez de Munain A, Mousavi P, Oksenberg J R, Baranzini SE (2007) Oksenberg and Sergio E. Baranzini. J Immunol, 179: 4074-4082

Christopher Siatskas and Claude C.A. Bernard (2007) Emerging treatments for Multiple Sclerosis. Australasian Science. 28: 18-22.

Huntington ND, Tomioka R, Clavarino C, Chow AM, Linares D, Mana P, Rossjohn J, Cachero, TG, Qian F, Kalled SL, Bernard CC, Reid HH. A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses. Int. Immunol. 2006; 18:1473-1485.

Azari MF, Profyris C, Karnezis T, Bernard CC, Small DH, Cheema SS, Ozturk E, Hatzinisiriou I, Petratos S Leukemia Inhibitory Factor Arrests Oligodendrocyte Death and Demyelination in Spinal Cord Injury. JNEN 2006; 65: 914-929

McQualter JL, Bernard CC.  Multiple Sclerosis: A battle between degeneration and repair. J. Neurochem. 2006:100:295-306.

Steinman, L., Martin, R., Bernard, C.C.A. Conlon, P. and Oksenberg, J.R.. Multiple Sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Ann. Rev. Neurosci. (2002) 25:491-505.

Wang, D.W., Ayers, M.M., Catmull. D.V., Hazelwood, L.J., Bernard, C.C.A. and J. M. Orian. Astrocyte associated axonal damage in pre-onset stages of experimental autoimmune encephalomyelitis. Glia. 2005; 51: 236-240.

Baranzini SE,  Bernard CCA Oksenberg JR. Modular transcriptional activity characterizes the initiation and progression of autoimmune encephalomyelitis.  J. Immunol..2005; 174:7412-7422.

Tara Karnezis, Wim Mandemakers, Jonathan L. McQualter, Binhai Zheng, Peggy P. Ho, Kelly A. Jordan, Belinda M. Murray, Ben Barres, Marc Tessier-Lavigne and Claude C.A. Bernard. The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination. Nature Neuroscience. 2004. 7: 736-744.

Mana, P., Goodyear, M., Bernard, C.C.A., Tomioka, R, Freire-Garabal, M, Linares, D. Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin. Int. Immunol. 2004,16:489-99.

William H. Robinson, Paulo Fontoura, Byung J. Lee, Henry E. Neuman de Vegvar, Jennifer Tom, Rosetta Pedotti, Carla D. DiGennaro, Dennis J. Mitchell, Derek Fong, Peggy P.-K. Ho,  Pedro J. Ruiz, Emanual Maverakis, David B. Stevens, Claude C.A. Bernard, Roland Martin, Vijay K. Kuchroo, Johannes M. van Noort, Claude P. Genain, Sandra Amor, Tomas Olsson,  Paul J. Utz, Hideki Garren, and Lawrence Steinman. Reverse genomics:  Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. (2003). Nature Biotech. 21: 1033-1039.

Clements, G. Reid, H.H. Tynan F. E., Beddoe, T. Perugini, M.A.  Bernard CCA & J.Rossjohn. (2003). The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis. (2003) Proc. Natl. Acad. Sci.  100:11059-11064.

Kennel De March, A., De Bouwerie, M., Béné, M.C., Gobert, B., Kolopp-Sarda, M.N. Faure,   G. and Bernard, C.C.A.  Myelin oligodendrocyte glycoprotein-specific B cell activtion and regulation in multiple sclerosis.(2003) J. Neuroimmunol.135: 117-125.

Okuda, Y., Okuda, M. and Bernard, C.C.A. Regulatory role of p53 in experimental autoimmune encephalomyelitis. (2003). J. Neuroimmunol.135:29-37.

Brundula, V., Rewcastle, N.B., Metz, L., Bernard, C.C.A., and Yong,V.W. Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis (2002). Brain 125:1297-1308.

Chabas, D., Baranzini, S.E., Mitchell, D., Bernard, C.C.A., Rittling, S, Denhardt, D., Sobel, R.A., Lock, C., Karpuj, M. Pedotti, R., Heller , R., Oksenberg, J.R. and Steinman, L. Osteopontin Influences Remission or Progression of Autoimmune Demyelinating Disease (2001). Science. 294: 1731-1735.

McQualter, J.L., Darwiche,R., Ewing, C., Onuki,M.,  Kay, T.W.,  Hamilton, J., Reid, H. and Bernard, C.C.A.  Granulocyte Macrophage Colony-Stimulating Factor: a New putative Therapeutic Target in Multiple Sclerosis. (2001). J. Exp. Med.  194: 873-881.

Hisahara, H., Araki, T., Sugiyama, F., Yagami, K., Suzuki, M.m Abe, K., Yamamura, K., Miyazaki, J., Momoi, T., Satura, T., Bernard, C.C.A., Okano, H., and Miura,M. Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against auto-immune- mediated demyelination. EMBO J. (2000) 19:341-348.

Baranzini,S.E., Jeong.M.C., Butunoi, C., Murray, R.S., Bernard, C.C.A. and           Oksenberg,.R. B cell repertoire and clonal expansion in Multiple Sclerosis brain lesions.   J.Immunol. (1999) 163:5133-5144.

Ichikawa,M.,Koh,C.S.,Hata,Y.,Inaba,Y.,Seki,C.,Inoue,A.,Itoh,M.,Ishihara,Y., Bernard, C.C.A. and Komiyama, A. IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice. Cellular Immunology (1999) 192:97-104.

Johns, T.G. and Bernard,C.C.A. The structure and function of myelin oligodendrocyte glycoprotein. J. Neurochem. (1999) 72:1-9.

Slavin, A., Ewing, C., Liu, J., Ichikawa, M., Slavin, J. and Bernard, C.C.A.  Induction of a Multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein. Autoimmunity. (1998) 28:109-120.

Okuda, Y., Bernard, C.C.A., Fujimura, H. ,Yanagihara,T. and Sakoda, S. Fas has a crucial role in the progression of experimental autoimmune encephalomyelitis. Mol. Immunol. (1998) 8:1667-1674.

Okuda,Y.,Sakoda,S., Bernard,C.C.A.and Yanagihara,T. The development ofautoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein is associated with an up-regulation of both proinflammatory and immunoregulatory cytokines in the central nervous system. J. Inter. Cytok. Res. (1998) 18:425-421.

Okuda, Y., Sakoda, S., Fujimura, H., Bernard, C.C.A., Saeki, Y., Kishimoto, T. and Yanagihara, T. IL-6 plays a crucial role in the induction of experimental autoimmune encephalomyelitis. Int. Immunol. (1998) 10:703-708.

Ewing, C and Bernard,C.C.A. Insights into the aetiology and the pathogenesis of multiple sclerosis. Immunol. Cell Biol. (1998) 76:47-54

Liu, J., Marino, M.W., Wong, G., Grail, D., Dunn, A., Bettadapura, J., Slavin, A.J., Old, L. and Bernard, C.C.A. TNF is a potent anti-inflammatory cytokine in autoimmune mediated demyelination. Nature Medicine. (1998) 4:78-83.

Hvas, J., Nouri, S., Kannourakis, G., McLean, C., Schall, T., Sinding, K., Justesen, J., Steinman, L., Oksenberg, J.R. and Bernard, C.C.A.  Perivascular T cells express the pro-inflammatory chemokine rantes in multiple sclerosis lesions. Scand.J.Immunol. (1997) 46: 195-203.

Johns, T.G. and Bernard, C.C.A.  Binding of complement component C1q to myelin oligodendrocyte glycoprotein: a novel mechanism for regulating CNS inflammation.  Mol. Immunol. (1997) 34: 33-38.

Bernard, C.C.A., Johns, T.G., Slavin, A.J., Ichikawa, M., Liu, J., Ewing, C. and Bettadapura, J.  Myelin oligodendrocyte glycoprotein, a novel candidate autoantigen in multiple sclerosis.  J. Mol. Med. (1997) 75: 89-94.

Slavin, A.J., Johns, T.G., Orian, J.M. and Bernard, C.C.A.  Regulation of myelin oligodendrocyte glycoprotein in different species throughout development.  Develop. Neurosci. (1997) 19: 69-78.

Sherritt, M.A., Tait, B., Varney, M., Kanaan, C., Stockman, A., Mackay, I.R., Muirden, K., Bernard, C.C.A. and Rowley, M.J.  Immunosusceptibility genes in rheumatoid arthritis.  Human Immunol. (1996) 51: 32-40.

Ichikawa, M., Johns, T.G., Adelmann, M. and Bernard, C.C.A.  Antibody response in Lewis rats injected with myelin oligodendrocyte glycoprotein derived peptides.  Int. Immunol. (1996) 8: 1667-1674.

Willenborg, D.O., Fordham, S., Bernard, C.C.A., Cowden, W.B. and Ramshaw, I.A.  Interferon-g plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein induced autoimmune encephalomyelitis. J. Immunol. (1996) 157: 3223-3227.

Johns, T.G., Kerlero de Rosbo, N., Menon, K.K., Abo, S., Gonzales, M.F. and Bernard, C.C.A.  Myelin oligodendrocyte glycoprotein induces a demyelinating encephalomyelitis resembling multiple sclerosis. J. Immunol. (1995) 154: 5536-5541.

Hilton, A.A., Slavin, A.J., Hilton, D.J. and Bernard, C.C.A.  Characterisation of cDNA and genomic clones encoding human myelin oligodendrocyte glycoprotein. J. Neurochem. (1995) 65: 309-318.