TONY N. MARION, Ph.D., M.S., B.S.

Professor, Molecular Sciences
Director, UTHSC Hepatitis C Cooperative Research Center
Director, UTHSC Flow Cytometry and Cell Sorting Laboratory

Office: 201F MOLECULAR SCIENCES BUILDING
858 MADISON AVENUE
MEMPHIS TN 381630000
Tel: (901) 448-6527
tmarion@uthsc.edu

Education

  • PostDoc, Yale University Medical School, New Haven, CT, Immunology
  • Kyoto University, Japan, Immunology
  • Ph.D., Univ. of Alabama at Birmingham, Birmingham, AL, Immunology
  • M.S., Wake Forest University, Winston-Salem, NC, Microbiology
  • B.S., North Carolina State University, Raleigh, NC, Chemistry

Research interest/specialty

Immune Tolerance in Anti-DNA Transgenic Lupus-Prone Mice.

Racial Difference in HCV-Host Interactions and Response to Therapy.

Research keywords

Anti-DNA, Lupus-Prone Mice, SLE, VH3H9, 3H9-m, JH locus, B cells, T cells, CD4 T cells, (NZB x NZW) F1 mice, glomerulonephritis

HCV-Host, HLA DR, interferon-alpha, Ribavarin therapy, African Americans, Caucasians, response rate, chronic hepatitis C

Research interest/specialty

Immune Tolerance in Anti-DNA Transgenic Lupus-Prone Mice. Racial Difference in HCV-Host Interactions and Response to Therapy.

Research keywords

Anti-DNA, Lupus-Prone Mice, SLE, VH3H9, 3H9-m, JH locus, B cells, T cells, CD4 T cells, (NZB x NZW) F1 mice, glomerulonephritis HCV-Host, HLA DR, interferon-alpha, Ribavarin therapy, African Americans, Caucasians, response rate, chronic hepatitis C

Research description

The major and longest funded area has been to understand the molecular and cellular bases for autoimmunity to DNA in mouse models for human systemic lupus erythematosus (SLE). This research employs anti-DNA antibody transgenic, genetically autoimmune-prone (NZB x NZW)F1 mice to analyze DNA-specific B cell tolerance and activation in an autoimmune background. The development of autoimmunity to DNA and lupus-like autoimmune disease in the normally autoimmune, lupus-prone (NZB x NZW)F1 mice depends upon whether the mice inherit the 3H9 anti-DNA heavy chain as a conventional IgM heavy-chain transgene (3H9-m) or as a VH3H9 heavy-chain variable region gene “knock-in” into the JH locus. 3H9-m transgenic (NZB x NZW)F1 do not produce anti-DNA autoantibodies and do not develop lupus nephritis. The VH3H9 knock-in transgenic (3H9R) (NZB x NZW)F1 mice develop autoimmune anti-DNA antibody and lupus nephritis similar to non transgenic (NZB x NZW)F1 mice. Tolerance to DNA in the conventional VH3H9 transgenic (NZB x NZW)F1 mice is a function of both B cells and T cells. B cell receptor-dependent stimulation is less effective in the conventional transgenic (NZB x NZW)F1 mice, and helper T cell activation is also less effective in the conventional transgenic (NZB x NZW)F1 mice. The latter deficiency may be the consequence of the anergic B cell environment in which CD4 T cells develop. Present and future research will take advantage of difference in autoimmune response between the two different transgenic (NZB x NZW)F1 to understand the cellular and molecular bases for autoimmune B cell activation in this important model for human SLE. A second project in this area of research involves analyses of pathogenic function of anti-DNA antibodies in lupus nephritis in mice and humans. The potential for monoclonal anti-DNA antibodies to passively induce glomerulonephritis appears to be independent of specificity for or binding to DNA or chromatin. The structural basis for pathogenic anti-DNA antibody function is being determined by proteomic analysis of mouse kidneys with passive experimentally induced disease. The other main area of research in my laboratory is immunity to hepatitis C virus in individuals chronically infected with hepatitis C. This project is part of the Center for Hepatitis C Research at UTHSC. The major focus of the Center’s research has been to understand the basis for racial differences in response to combination pegylated interferon-alpha and Ribavarin therapy for chronic hepatitis C. African Americans have only a 26% response rate, determined as sustained clearance of circulating virus, compared to 56% for Caucasians. Recent results from our clinical research also indicate a much higher frequency of a particular HLA DR allele among chronically infected African Americans at our Center. Present and future studies are directed toward understanding the relevance of the increased frequency of HLA DR among chronically infected Afrcrican Americans. Ongoing research will also seek to determine how differences in immune responses may or may not be related to differences in response to therapy between chronically infected African American and Caucasian individuals.

Publications

  1. Lavine, CL, Clinton, SR, Angelova-Fischer, I, Marion, TN, Bina, XR, Bina, JE, Whitt, MA, Miller, MA. Immunization with heat-killed Francisella tularensis LVS elicits protective antibody-mediated immunity. Eur J Immunol, 37 (11), 3007-20, 2007.
  2. Steeves, MA, Marion, TN. Tolerance to DNA in (NZB x NZW)F1 mice that inherit an anti-DNA V(H) as a conventional micro H chain transgene but not as a V(H) knock-in transgene. J Immunol, 172 (11), 6568-77, 2004.
  3. Marion, TN, Krishnan, MR, Steeves, MA, Desai, DD. Affinity maturation and autoimmunity to DNA. Curr Dir Autoimmun, 6, 123-53, 2002.
  4. Desai, DD, Marion, TN. Induction of anti-DNA antibody with DNA-peptide complexes. Int Immunol, 12 (11), 1569-78, 2000.
  5. Sangster, MY, Topham, DJ, D'Costa, S, Cardin, RD, Marion, TN, Myers, LK, Doherty, PC. Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. J Immunol, 164 (4), 1820-8, 2000.
  6. Ruckenstein, MJ, Sarwar, A, Hu, L, Shami, H, Marion, TN. Effects of immunosuppression on the development of cochlear disease in the MRL-Fas(lpr) mouse. Laryngoscope, 109 (4), 626-30, 1999.
  7. Wilkinson, DA, Fitzgerald, TJ, Marion, TN, Carlson, GM. Mg2+ induces conformational changes in the catalytic subunit of phosphorylase kinase, whether by itself or as part of the holoenzyme complex. J Protein Chem, 18 (2), 157-64, 1999.
  8. Krishnan, MR, Marion, TN. Comparison of the frequencies of arginines in heavy chain CDR3 of antibodies expressed in the primary B-cell repertoires of autoimmune-prone and normal mice. Scand J Immunol, 48 (3), 223-32, 1998.
  9. Wilkinson, DA, Norcum, MT, Fizgerald, TJ, Marion, TN, Tillman, DM, Carlson, GM. Proximal regions of the catalytic gamma and regulatory beta subunits on the interior lobe face of phosphorylase kinase are structurally coupled to each other and with enzyme activation. J Mol Biol, 265 (3), 319-29, 1997.
  10. Wang, M, Desai, D, Marion, TN. T cells specific for DNA-binding peptides. Lupus, 6 (3), 349-50, 1997.
  11. Marion, TN, Krishnan, MR, Desai, DD, Jou, NT, Tillman, DM. Monoclonal anti-DNA antibodies: structure, specificity, and biology. Methods, 11 (1), 3-11, 1997.
  12. Brand, DD, Marion, TN, Myers, LK, Rosloniec, EF, Watson, WC, Stuart, JM, Kang, AH. Autoantibodies to murine type II collagen in collagen-induced arthritis: a comparison of susceptible and nonsusceptible strains. J Immunol, 157 (11), 5178-84, 1996.
  13. Krishnan, MR, Jou, NT, Marion, TN. Correlation between the amino acid position of arginine in VH-CDR3 and specificity for native DNA among autoimmune antibodies. J Immunol, 157 (6), 2430-9, 1996.
  14. Ye, XJ, Marion, TN, Terato, K, Aelion, JA, Cremer, MA, Tillman, DM, Krug, MS, Jackson, B, Yoo, TJ. Variable-region gene family usage for type II collagen autoantibodies in arthritis-susceptible DBA/1 mice. Clin Immunol Immunopathol, 78 (3), 263-75, 1996.
  15. Marion, TN, Tillman, DM, Krishnan, MK, Desai, DD, Jou, NT, Ruff, MB. Immunoglobulin variable-region structures in immunity and autoimmunity to DNA. Tohoku J Exp Med, 173 (1), 43-63, 1994.
  16. Wilkinson, DA, Marion, TN, Tillman, DM, Norcum, MT, Hainfeld, JF, Seyer, JM, Carlson, GM. An epitope proximal to the carboxyl terminus of the alpha-subunit is located near the lobe tips of the phosphorylase kinase hexadecamer. J Mol Biol, 235 (3), 974-82, 1994.
  17. Desai, DD, Krishnan, MR, Swindle, JT, Marion, TN. Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol, 151 (3), 1614-26, 1993.
  18. Krishnan, MR, Marion, TN. Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. J Immunol, 150 (11), 4948-57, 1993.
  19. Tillman, DM, Jou, NT, Hill, RJ, Marion, TN. Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med, 176 (3), 761-79, 1992.
  20. Marion, TN, Tillman, DM, Jou, NT, Hill, RJ. Selection of immunoglobulin variable regions in autoimmunity to DNA. Immunol Rev, 128, 123-49, 1992.
  21. Marion, TN, Tillman, DM, Jou, NT. Interclonal and intraclonal diversity among anti-DNA antibodies from an (NZB x NZW)F1 mouse. J Immunol, 145 (7), 2322-32, 1990.