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Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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Cong. John E. Porter Professor of Microbiology-
Immunology; Director, Immunobiology Center
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
A. Positions and Honors:
NIH Postdoctoral Research Fellow (with Henry N. Claman, M.D.), Univ. of Colorado Health Sci. Ctr.,
Instructor, Department of Medicine, Division of Clinical Immunology, Univ. of Colorado Health Sciences Ctr.,
Assistant Professor, Departments of Medicine and of Microbiology-Immunology, Univ. of Colorado Health
Department of Microbiology-Immunology, Northwestern Univ. Medical School, Chicago, IL, – Professor and
Director of The Interdepartmental Immunobiology Center (9/92-Present); Congressman John E. Porter Professor (10/00-Present): Associate Professor (9/86-8/92); Assistant Professor (7/81-8/86)
USPHS Air Pollution Control Graduate Fellowship, 6/69-6/70 & 6/72-6/73 NIH Individual Post Doctoral Fellowship (AI-05593) 10/77-7/78 NIH Young Investigator Award (AI-14913) 8/78-7/81 Member - Honor Society of Phi Kappa Phi (1975); Am. Society for Microbiology (1975); Am. Association of
Immunologists (1977); Chicago Association of Immunology (1981); International Society of Neuroimmunology (1987); Am. Assoc. Advancement of Science (1986), Society for Neuroscience (2006)
Editorial Board - J. Immunology
(1982-85, Section Editor: 1995-2000); Regional Immunology
(2001-Present); Cellular Immunology
(Deputy Editor, 1999-Present); Viral Immunology
(2000-Present); J. Autoimmunity
Ad Hoc Reviewer - NINDS Site Visitor, Immunological Sciences and Neurology C Study Sections, National
Science Foundation, Veterans Administration, Science
, J. Immunology
, Regional Immunology
, J. Neuroimmunol., J. Virology, J. Clin. Invest., Immunity, J. Exp. Medicine, Nature Med.
HHMI/NSF Predoctoral Fellowship Immunology and Cell Biology Review Committee (1999-2003, Chair
NIH Neurology C/Neurologic Sciences 3 (NLS 3) Study Section, Regular Member (9/93-6/97) National Multiple Sclerosis Society Study Section Panel B, Regular Member (1/98-12/03) NIH – ‘Immune Tolerance Network’ Steering Committee: 11/01-Pres. Juvenile Diabetes Research Foundation (JDRF) Immunology Study Section: 01/04-Pres. National Multiple Sclerosis Society ‘Fast Forward’ Scientific and Business Advisory Committee: 01/08-Pres. American Association of Immunologists – Publications Committee: 2000-04 (Chair, 2002-04); Council (Ad
Pennsylvania State University, Eberly College of Science Outstanding Alumni Science Award: September,
Fellow of the American Association for the Advancement of Science, Elected 10/04 Fellow of the American Academy of Microbiology, Elected 05/07
B. Relevant Peer-Reviewed Publications (selected from 276 total published and in press papers):
McRae, B. L., C. L. Vanderlugt, M. C. Dal Canto, and S. D. Miller.
1995. Functional evidence for epitope
spreading in the relapsing pathology of EAE in the SJL/J mouse. J. Exp. Med. 182:75-85.
Miller, S. D., C. L. Vanderlugt, D. J. Lenschow, J. G. Pope, N. J. Karandikar, M. C. Dal Canto, and J. A.
1995. Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of
murine EAE. Immunity. 3:739-745.
Miller, S. D., C. L. Vanderlugt, W. Smith Begolka, W. Pao, R. L. Yauch, K. L. Neville, Y. Katz-Levy, A.
Carrizosa, and B. S. Kim.
1997. Persistent CNS infection with Theiler’s virus leads to myelin-specific
autoimmunity via epitope spreading. Nature Med. 3:1133-1136.
Katz-Levy, Y., K. L. Neville, J. Padilla, S. M. Rahbe, W. S. Begolka, A. M. Girvin, J.K. Olson, C. L.
Vanderlugt, and S. D. Miller.
2000. Temporal development of autoreactive Th1 responses and
endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus-infected mice. J.
Vanderlugt, C. L., T. N. Eagar, K. L. Neville, K. M. Nikcevich, J. A. Bluestone, and S. D. Miller.
Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J. Immunol. 164:670-678
Olson, J. K., A. M. Girvin, and S. D. Miller.
2001. Direct activation of innate and antigen presenting
functions of microglia following infection with Theiler’s virus. J. Virol. 75:9780-9789
Vanderlugt, C. L. and S. D. Miller.
2002. Role of epitope spreading in immune-mediated diseases:
Implications for immunotherapy. Nat. Rev. Immunol. 2:85-95.
Tompkins, S. M. and S. D. Miller.
2002. An array of possibilities for MS. Nat. Med. 8:451-453. Neville, K. L., J. Padilla, L. A. Matis, and S. D. Miller.
2002. Myelin-specific tolerance attenuates the
progression of a virus-induced demyelinating disease: Implications for the treatment of MS. J. Neuroimmunol. 123:18-29.
Croxford, J. L., J. K. Olson, and S. D. Miller.
2002. Epitope spreading and molecular mimicry as triggers of
autoimmunity in the Theiler’s virus-induced demyelinating disease model of multiple sclerosis.
Girvin, A. M., K. B. Gordon, C. J. Welsh, and S. D. Miller.
2002. Differential abilities of CNS-resident
endothelial cells and astrocytes to serve as inducible antigen presenting cells. Blood. 99:3692-3701.
Kohm, A. P., P. A. Carpentier, H. A. Anger, and S. D. Miller.
2002. Cutting Edge:
regulatory cells suppress antigen-specific autoreactive immune responses and CNS inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169:4712-4716.
Mack, C. L., C. L. Vanderlugt-Castaneda, K. L. Neville, and S. D. Miller.
2003. Microglia are activated to
become competent antigen presenting cells and potent effector cells in the inflammatory environment of the Theiler’s virus model of multiple sclerosis. J. Neuroimmunol. 144:68-79.
Howard, L. M., K. L. Neville, L. M. Haynes, M.C. Dal Canto, and S. D. Miller.
2003. CD154 blockade
results in transient reduction in TMEV-induced demyelinating disease. J. Virol. 77:2247-2250.
Olson, J. K. and S. D. Miller.
2004. Microglia initiate CNS innate and adaptive immune responses through
multiple Toll-like receptors. J. Immunol. 173:3916-3924.
Carpentier, P. A., W. S. Begolka, J. K. Olson, A. Elhofy, W. J. Karpus, and S. D. Miller.
activation of astrocytes by innate and adaptive immune stimuli. Glia 49:360-374.
McMahon, E. J., S. L. Bailey, C. L. Vanderlugt-Castenada, H. Waldner, and S. D. Miller.
spreading initiates in the CNS in two mouse models of multiple sclerosis. Nature Med. 11:335-339.
*Croxford, J. L., J. K. Olson*, H. A. Anger, and S. D. Miller.
2005. Initiation and exacerbation of CNS
autoimmune demyelination via virus-induced molecular mimicry: Implications for MS pathogenesis. J. Virol. 79:8581-8590.
Smith, C. E., T. N. Eagar, J. Strominger, and S. D. Miller.
2005. Differential induction of IgE-mediated
anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 102:9595-9600.
Melvold, R. W. and S. D. Miller.
2005. Immunogenetics/resistance/susceptibility to Theiler’s virus infection.
In: Experimental Models of Multiple Sclerosis
(E. Lavi and S. Constantinescu, eds.). Kulwer Academic Publishers, London. Pp. 629-644
Kohm, A. P., J. S. Williams, A. L. Bickford, J. S. McMahon, L. Chatenoud, J. F. Bach, J. A. Bluestone,
and S. D. Miller.
2005. Treatment with non-mitogenic anti-CD3 antibody induces CD4+ T cell
unresponsiveness and functional reversal of established autoimmune disease. J. Immunol
Kohm, A. P., J. S. McMahon, J. R. Podojil, W. Smith Begolka, M. Degutes, D. J. Kasprowicz, S. F.
Ziegler, and S. D. Miller
. 2006. Cutting Edge:
Anti-CD25 monoclonal antibody injection results in the
functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J. Immunol. 176:3301-3305.)
Bailey, S. L., P. A. Carpentier, E. J. McMahon, W.S. Begolka, and S. D. Miller.
2006. Innate and adaptive
immune responses of the central nervous system. Crit. Rev. Immunol. 26:149-188.
Ercolini, A. M. and S. D. Miller.
2006. Brief Review:
Mechanisms of immunopathology in murine models of
CNS demyelinating disease. J. Immunol. 176:3293-3298.
Lin, W., S. L. Bailey, H. Ho, H. P. Harding, D. Ron, S. D. Miller, and B. Popko.
2007. The integrated stress
response protects oligodendrocytes against immune-mediated demyelination. J. Clin. Invest. 117:448-456.
Balabanov, R., K. Strand, R. Goswami, E. McMahon, W. Smith Begolka, S. D. Miller, and B. Popko.
2007. Interferon-gamma-oligodendrocyte interactions in the regulation of EAE. J. Neurosci. 27:2013-2024.
Carpentier, P. A., B. R. Williams, and S. D. Miller.
2007. Distinct roles of PKR and TLR3 in the activation of
astrocytes by viral stimuli. Glia. 55:239-252
Schreiner, B., S. M. Bailey, and S. D. Miller.
2007. T cell response dynamics in animal models of multiple
sclerosis: Implications for immunotherapies. Expert Rev. Clin. Immunol. 3:57-72.
Turley, D. M. and S. D. Miller.
2007. Peripheral tolerance induction using ECDI-fixed APCs uses both direct
and indirect mechanisms of antigen presentation for prevention of EAE. J. Immunol. 178:2212-2220.
Bailey, S. L., B. Schreiner, E. J. McMahon, and S. D. Miller.
2007. CNS myeloid dendritic cells presenting
endogenous myelin peptides preferentially polarize CD4+ Th17 cells in relapsing EAE. Nat. Immunol. 8:172-180.
Teague Getts, M. T., B. S. Kim, and S. D. Miller.
2007. Differential outcome of tolerance induction in naïve
vs. activated Theiler’s virus epitope-specific CD8+ cytotoxic T cells. J. Virol. 81:6584-6593.
Miller, S. D., D. M. Turley, and J. R. Podojil.
2007. Antigen-specific tolerance strategies for the prevention
and treatment of autoimmune disease. Nat. Rev. Immunol. 7:665-677.
Ercolini, A. M. and S. D. Miller.
2007. Molecular mimics can induce novel self peptide-reactive CD4+ T
clonotypes in autoimmune disease. J. Immunol. 179:6604-6612
*Carpentier, P. A., D. S. Duncan*, and S. D. Miller.
2008. Glial Toll-like receptor signaling in central nervous
system infection and autoimmunity. Brain Behav. Immun. 22:140-147.
Carpentier, P. A. and S. D. Miller.
2008. Pro-inflammatory functions of astrocytes correlate with viral
clearance and strain-dependent protection from TMEV-induced demyelinating disease. Virology. In press.
Bailey-Bucktrout, S. L., S. Caulkins, G. Goings, J. A. Fischer, A. Dzionek, and S. D. Miller.
CNS plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune
encephalomyelitis. J. Immunol. In press
C. Research Support:
ONGOING RESEARCH SUPPORT
Pathogenesis and Immunoregulation of PLP-Induced R-EAE Examines: (1) temporal progression, effector role, TCR repertoire, and epitope spreading of peripheral and CNS Th1/Th2 responses in mice with relapsing, chronic and acute EAE; and (2) peripheral and CNS-resident APC population involved in presenting endogenous myelin epitopes to naïve and activated T cells in EAE
National Multiple Sclerosis Society (S. D. Miller, P. I.) Pathogenesis and Immunoregulation of PLP-Induced R-EAE 80% overlap with NIH NS-030871-14 above - provides a supplement to support 75% of a research tech.
NIH (S.D. Miller, P.I.) Immunoregulation and Pathology of Chronic-Relapsing EAE Examines: (1) in vivo
mechanisms responsible for Ag-SP tolerance induced by peptide-pulsed, ECDI-fixed APCs; (2) direct effects of in vitro
tolerogenic vs. immunogenic encounter on Th1/Th2/Th17 cytokine production and induction of CD+CD25+Foxp3+ Treg cells; and (3) effects of Ag-SP tolerance on signaling events in APCs and tolerized T cells.
NMSS (S.D. Miller, P.I.) Immunoregulation and Pathology of Chronic-Relapsing EAE 90% overlap with NIH R01 NS-026543-18 above – provides supplement to support a postdoctoral fellow.
NIH/NINDS (S. D. Miller, P. I.) Mechanisms of CD4+CD25+ T Regulatory Cells in EAE
Examines: (1) role of CD4+CD25+ Treg cells in modulating the initiation and progression of EAE; (2) contribution of CD4+CD25+ Tregs to age-, gender-, and strain-associated susceptibility to EAE; and (3) mechanism by which CD4+CD25+ Tregs influence T cell activation, expansion and/or effector function.
NIH/NINDS (S. D. Miller, P. I.)
A Virus-Induced Molecular Mimicry Model of MS
Examines: (1) efficiency of autoreactive T cell activation, T cell repertoire, and induction of demyelinating disease
following infection with TMEV and non-neurotropic viruses encoding molecular mimics of PLP139-151; (2)
activation/regulation of autoimmune responses and clinical disease in humanized HLA-DR2b/MBP85-99-specific TcR Tg
mice with TMEV encoding mimics of MBP85-99; and (3) activation of autoimmune responses and clinical disease in SJL
m e following infection with H. influenzae
expressing a natural mimic of PLP139-151.
NIH/NINDS (S.D. Miller, Program Director and PI Project 1 + Admin. Core A + Histopathology Core C) CNS Damage from Theiler’s Virus Persistence: MS Model PPG examines the molecular pathogenesis and immunopathogenesis of TMEV-induced demyelinating disease. Project 1 aims are (1) to examine the effector role, T cell receptor repertoire usage, and fine antigenic specificity of peripheral virus- and neuroantigen-specific immune responses at varying times following TMEV infection (2) analysis of T cell specificity and APC function of CNS-infiltrating T cells in TMEV-infected mice (3) efficacy, specificity and molecular mechanisms of regulation of virus-induced demyelination using specific tolerance and antagonists of B7/CD28-mediated costimulation.
Myelin Repair Foundation (S. D. Miller, P. I.)
Promotion of Oligodendrocyte Regeneration and CNS Remyelination
Examines: (1) the temporal expression of myelin genes during R-EAE and TMEV-IDD; (2) temporal and spatial
expression of molecules important in directing and/or regulating myelination/re-myelination (e.g.,
Notch family members,
Jagged, Serrate, Sonic hedgehog, BMP4, CxCL1, CxCR2) during R-EAE and TMEV-IDD; (3) the effect of γ-secretase
(Notch) inhibitors on the course of EAE and TMEV-induced demyelinating disease; and (4) treatment of EAE combining
regulation with drugs enhancing myelin repair.
04/01/06-03/31/09 No-Cost Ext.
Fidelity Foundation (S. D. Miller, P. I.) Role of Specific Immunoregulation and Oligodendrocyte Stem Cell Transfer in Promoting Clinical Disease Amelioration and Remyelination in EAE Examines: (1) immunological and (2) neurobiological effects of GFP-labeled neurospheres in mice with R-EAE and C-EAE; and (3) combined effects of immunoregulation and stem cell therapy in R-EAE and C-EAE.
CombinatoRx, Inc. (S. D. Miller, P. I.)
Combination Therapy of R-EAE with Nortiptyline and Desloratadine
Examines effects of combination therapy of R-EAE with nortiptyline and desloratadine on R-EAE.
04/01/04-03/31/08 No Cost Ext.
National Multiple Sclerosis Society (S. D. Miller, P. I.) Understanding the Role of Gamma/Delta T Cells in Relapsing EAE Examines: (1) peripheral γδ T cell responses in EAE and their migration to and function in the CNS; (2) influence of γδ T cells on encephalitogenic T cell responses and EAE induction; and (3) mechanisms by with γδ T cells modulate αβ CD4+ encephalitogenic T cells.
Juvenile Diabetes Res. Foundation (S. D. Miller, P. I.) Creating an Immune Privileged Site for Islet Transplantation Examines: (1) efficacy of ECDI-fixed cell tolerance for islet and allo-antigens for the treatment of T1D in NOD mice and for
ction of tolerance to allogeneic islets; (2) role of ex vivo
-induced Tregs in allogeneic islet cell transplantation
2 T32 AI-0007476-09-11A1
NIH/NIAID (S. D. Miller, P. I.) Immunology and Molecular Pathogenesis Training Program
Section 2.10 Transportation Submitter Name/ Plan Provision Summary of Submission Decision Requested Submission No. and Point C E Henderson Support generally the Section 32 analysis. Request more government funding for Southlands „Roads of National Importance‟. To Request retention of Objectives and Policies. maintain safety and resilience, also restoration
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