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Christopher Norbury

TitleProfessor
InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive Hershey PA 17033
Mailbox: H107
Phone7175317204

 Overview 
 overview
PREFERRED TITLE/ROLE:

Professor Microbiology and Immunology

GRADUATE PROGRAM AFFILIATIONS:

Microbiology and Immunology, Cell and Molecular Biology, Integrative Biosciences

EDUCATION:

Ph.D., University of Dundee, Scotland, UK, 1996
Postdoctoral Training, National Institute of Allergy and Infectious Diseases, Bethesda, MD, 1996-2001

NARRATIVE:

Antigen Presentation In Induction of an Anti-Viral CD8+ T Cell Response


CD8+ T cells are a major component of the cellular response to viral infection. These cells generally recognize peptides derived from viral proteins in complex with host MHC Class I molecules. The major focus of my laboratory is to elucidate the mechanism by which these peptides are generated in a natural viral infection. Knowledge of the pathways of presentation of these peptides will allow the rational design anti-viral and anti-tumor vaccines allowing generation of CD8+ T cells responses via more natural, and therefore more efficient, pathways.


To this end we are investigating which cells must present antigen in vivo for efficient activation of CD8+ T cells. The localization and timing of peptide presentation, as well as the properties of the antigen-presenting cell are all areas under current investigation in a number of viral systems. Other questions include whether these cells must be infected for efficient generation of peptides recognized by CD8+ T cells, and how the requirements differ between the same antigens encoded in different viruses.


The Effects of Psychological Stress Upon Antigen Presentation and Dendritic Cell Function


In a collaboration with Drs Emmy Truckenmiller and Robert Bonneau we investigate the effects of stress hormones, such as corticosterone (cortisol), upon both antigen presentation and dendritic cell (DC) phenotype and function in vitro and in vivo. Stress is immunosuppressive and the CD8+ T cell response to viral infection is dramatically reduced in stressed individuals. DC are cells that are likely vital for the induction of CD8+ T cell responses, so information about their phenotype under stressed conditions, as well as the efficiency of antigen presentation, will provide significant information for the treatment of many pathologies that are worsened with stress.





 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Rubio D, Xu RH, Remakus S, Krouse TE, Truckenmiller ME, Thapa RJ, Balachandran S, Alcamí A, Norbury CC, Sigal LJ. Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection. Cell Host Microbe. 2013 Jun 12; 13(6):701-10.
    View in: PubMed
  2. Xu RH, Rubio D, Roscoe F, Krouse TE, Truckenmiller ME, Norbury CC, Hudson PN, Damon IK, Alcamí A, Sigal LJ. Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver. PLoS Pathog. 2012 Jan; 8(1):e1002475.
    View in: PubMed
  3. Heuss ND, Lehmann U, Norbury CC, McPherson SW, Gregerson DS. Local activation of dendritic cells alters the pathogenesis of autoimmune disease in the retina. J Immunol. 2012 Feb 1; 188(3):1191-200.
    View in: PubMed
  4. Fischer MA, Davies ML, Reider IE, Heipertz EL, Epler MR, Sei JJ, Ingersoll MA, Rooijen NV, Randolph GJ, Norbury CC. CD11b?, Ly6G? cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection. PLoS Pathog. 2011 Nov; 7(11):e1002374.
    View in: PubMed
  5. Hunzeker JT, Elftman MD, Mellinger JC, Princiotta MF, Bonneau RH, Truckenmiller ME, Norbury CC. A marked reduction in priming of cytotoxic CD8+ T cells mediated by stress-induced glucocorticoids involves multiple deficiencies in cross-presentation by dendritic cells. J Immunol. 2011 Jan 1; 186(1):183-94.
    View in: PubMed
  6. Schell AM, Granger EL, Koczot F, Fischer MA, Norbury CC. Dendritic cell migration limits the duration of CD8+ T-cell priming to peripheral viral antigen. J Virol. 2010 Apr; 84(7):3586-94.
    View in: PubMed
  7. Elftman MD, Hunzeker JT, Mellinger JC, Bonneau RH, Norbury CC, Truckenmiller ME. Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function. J Immunol. 2010 Feb 15; 184(4):1867-75.
    View in: PubMed
  8. Gulani J, Norbury CC, Bonneau RH, Beckwith CS. The effect of Helicobacter hepaticus infection on immune responses specific to herpes simplex virus type 1 and characteristics of dendritic cells. Comp Med. 2009 Dec; 59(6):534-44.
    View in: PubMed
  9. Hong EG, Ko HJ, Cho YR, Kim HJ, Ma Z, Yu TY, Friedline RH, Kurt-Jones E, Finberg R, Fischer MA, Granger EL, Norbury CC, Hauschka SD, Philbrick WM, Lee CG, Elias JA, Kim JK. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes. 2009 Nov; 58(11):2525-35.
    View in: PubMed
  10. Tewalt EF, Grant JM, Granger EL, Palmer DC, Heuss ND, Gregerson DS, Restifo NP, Norbury CC. Viral sequestration of antigen subverts cross presentation to CD8(+) T cells. PLoS Pathog. 2009 May; 5(5):e1000457.
    View in: PubMed
  11. English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippé R, Desjardins M. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol. 2009 May; 10(5):480-7.
    View in: PubMed
  12. Tewalt EF, Maynard JC, Walters JJ, Schell AM, Berwin BL, Nicchitta CV, Norbury CC. Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo. Immunology. 2008 Dec; 125(4):480-91.
    View in: PubMed
  13. Elftman MD, Norbury CC, Bonneau RH, Truckenmiller ME. Corticosterone impairs dendritic cell maturation and function. Immunology. 2007 Oct; 122(2):279-90.
    View in: PubMed
  14. Fischer MA, Tscharke DC, Donohue KB, Truckenmiller ME, Norbury CC. Reduction of vector gene expression increases foreign antigen-specific CD8+ T-cell priming. J Gen Virol. 2007 Sep; 88(Pt 9):2378-86.
    View in: PubMed
  15. Reiley WW, Jin W, Lee AJ, Wright A, Wu X, Tewalt EF, Leonard TO, Norbury CC, Fitzpatrick L, Zhang M, Sun SC. Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. J Exp Med. 2007 Jun 11; 204(6):1475-85.
    View in: PubMed
  16. Zhang B, Ramesh G, Norbury CC, Reeves WB. Cisplatin-induced nephrotoxicity is mediated by tumor necrosis factor-alpha produced by renal parenchymal cells. Kidney Int. 2007 Jul; 72(1):37-44.
    View in: PubMed
  17. Fischer MA, Norbury CC. Initiation of primary anti-vaccinia virus immunity in vivo. Immunol Res. 2007; 37(2):113-33.
    View in: PubMed
  18. Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS, Kester M, Kimball SR, Krady JK, LaNoue KF, Norbury CC, Quinn PG, Sandirasegarane L, Simpson IA. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes. 2006 Sep; 55(9):2401-11.
    View in: PubMed
  19. Donohue KB, Grant JM, Tewalt EF, Palmer DC, Theoret MR, Restifo NP, Norbury CC. Cross-priming utilizes antigen not available to the direct presentation pathway. Immunology. 2006 Sep; 119(1):63-73.
    View in: PubMed
  20. Norbury CC, Tewalt EF. Upstream toward the "DRiP"-ing source of the MHC class I pathway. Immunity. 2006 May; 24(5):503-6.
    View in: PubMed
  21. Norbury CC. Drinking a lot is good for dendritic cells. Immunology. 2006 Apr; 117(4):443-51.
    View in: PubMed
  22. Truckenmiller ME, Bonneau RH, Norbury CC. Stress presents a problem for dendritic cells: corticosterone and the fate of MHC class I antigen processing and presentation. Brain Behav Immun. 2006 May; 20(3):210-8.
    View in: PubMed
  23. Reiley WW, Zhang M, Jin W, Losiewicz M, Donohue KB, Norbury CC, Sun SC. Regulation of T cell development by the deubiquitinating enzyme CYLD. Nat Immunol. 2006 Apr; 7(4):411-7.
    View in: PubMed
  24. Truckenmiller ME, Princiotta MF, Norbury CC, Bonneau RH. Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation. J Neuroimmunol. 2005 Mar; 160(1-2):48-60.
    View in: PubMed
  25. Mostoller K, Norbury CC, Jain P, Wigdahl B. Human T-cell leukemia virus type I Tax induces the expression of dendritic cell markers associated with maturation and activation. J Neurovirol. 2004 Dec; 10(6):358-71.
    View in: PubMed
  26. Truckenmiller ME, Norbury CC. Viral vectors for inducing CD8+ T cell responses. Expert Opin Biol Ther. 2004 Jun; 4(6):861-8.
    View in: PubMed
  27. Norbury CC, Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, Bennink JR, Yewdell JW. CD8+ T cell cross-priming via transfer of proteasome substrates. Science. 2004 May 28; 304(5675):1318-21.
    View in: PubMed
  28. Kranc KR, Bamforth SD, Bragança J, Norbury C, van Lohuizen M, Bhattacharya S. Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Mol Cell Biol. 2003 Nov; 23(21):7658-66.
    View in: PubMed
  29. Norbury CC, Sigal LJ. Cross priming or direct priming: is that really the question? Curr Opin Immunol. 2003 Feb; 15(1):82-8.
    View in: PubMed
  30. Norbury CC, Malide D, Gibbs JS, Bennink JR, Yewdell JW. Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat Immunol. 2002 Mar; 3(3):265-71.
    View in: PubMed
  31. Wang B, Norbury CC, Greenwood R, Bennink JR, Yewdell JW, Frelinger JA. Multiple paths for activation of naive CD8+ T cells: CD4-independent help. J Immunol. 2001 Aug 1; 167(3):1283-9.
    View in: PubMed
  32. Chen W, Norbury CC, Cho Y, Yewdell JW, Bennink JR. Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens. J Exp Med. 2001 Jun 4; 193(11):1319-26.
    View in: PubMed
  33. Prasad SA, Norbury CC, Chen W, Bennink JR, Yewdell JW. Cutting edge: recombinant adenoviruses induce CD8 T cell responses to an inserted protein whose expression is limited to nonimmune cells. J Immunol. 2001 Apr 15; 166(8):4809-12.
    View in: PubMed
  34. Norbury CC, Princiotta MF, Bacik I, Brutkiewicz RR, Wood P, Elliott T, Bennink JR, Yewdell JW. Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. J Immunol. 2001 Apr 1; 166(7):4355-62.
    View in: PubMed
  35. Norbury CC. Tracing the route taken by peptides and major histocompatibility complex class I molecules in presentation of exogenous antigens. Methods Mol Biol. 2001; 156:33-48.
    View in: PubMed
  36. Gretz JE, Norbury CC, Anderson AO, Proudfoot AE, Shaw S. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J Exp Med. 2000 Nov 20; 192(10):1425-40.
    View in: PubMed
  37. Schubert U, Antón LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000 Apr 13; 404(6779):770-4.
    View in: PubMed
  38. Yewdell JW, Norbury CC, Bennink JR. Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: implications for generating CD8+ T cell responses to infectious agents, tumors, transplants, and vaccines. Adv Immunol. 1999; 73:1-77.
    View in: PubMed
  39. Norbury CC, Chambers BJ, Prescott AR, Ljunggren HG, Watts C. Constitutive macropinocytosis allows TAP-dependent major histocompatibility complex class I presentation of exogenous soluble antigen by bone marrow-derived dendritic cells. Eur J Immunol. 1997 Jan; 27(1):280-8.
    View in: PubMed
  40. Norbury CC, Hewlett LJ, Prescott AR, Shastri N, Watts C. Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages. Immunity. 1995 Dec; 3(6):783-91.
    View in: PubMed
  41. Gorczynski RM, Norbury C. Immunity to murine sarcoma virus induced tumours. 3. Analysis of the cell populations involved in protection from lethal tumour progression of sublethally irradiated, MSV inoculated, mice. Br J Cancer. 1974 Aug; 30(2):118-28.
    View in: PubMed
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