MARKO Z. RADIC, Ph.D.

Associate Professor
Department of Microbiology, Immunology and Biochemistry

Office: 211 MOLECULAR SCIENCES BUILDING
858 MADISON AVENUE
MEMPHIS TN 381632129
Tel: (901) 448-8219
mradic@uthsc.edu
https://www.uthsc.edu/molecular_sciences/directories/faculty/m_radic.php

Education

  • PostDoc, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, Structure-Function Analysis of Anti-DNA Autoantibodies
  • Ph.D., University of California at Irvine, Irvine, CA, Biological Sciences
  • B.S., University of California at Davis, Davis, CA, Genetics

My Current Curriculum Vitae

Research description

Work in the Radic laboratory centers on the mechanisms leading to autoimmune disease, with an emphasis on antibody-mediated disorders, such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Anti-Phospholipid Syndrome (APS). The lab studies autoantibodies from patients as well as mouse strains that develop autoimmunity resembling the human disorders. In the lab, molecular details of antibody binding to antigens are explored. For this purpose, autoantibodies are expressed from hybridoma cell lines, or as recombinant antibody fragments in heterologous systems. Recent discoveries from the Radic lab include the identification of histone deimination, a post-translational modification of a major nuclear autoantigen, in neutrophil granulocytes exposed to inflammatory stimuli. The identification of autoantibodies to deiminated histones provided a link between innate immunity to infection and the induction of autoimmunity, a process that is still mysterious. In ongoing experiments, we have obtained initial evidence for the beneficial effect of an immunotherapy that has been applied to the treatment of B cell leukemia.  Cytotoxic T cells were transduced with recombinant genes encoding an engineered (chimeric) antigen receptor (CAR) that directed the CAR T cells to thoroughly and persistently deplete CD19 B cells.  In lupus mice treated by this method, disease was ameliorated and lifetimes were extended.  We hope that our discoveries will be useful in designing and testing methods for inhibiting the ill effects of autoantibodies in lupus, and that our findings will find applications in the therapy of autoimmune disease.

Research interest/specialty

Molecular Mechanisms of Autoimmune Diseases and Discovery of Cures for Lupus

Research keywords

Autoantibodies,
Autoimmunity,
B Cell Development,
Neutrophils,
Histones,
Post-translational modifications,
Chimeric antigen receptors (CARs),
Cytotoxic T cells

Publications

  1. Boeltz S, Amini P, Anders HJ, Andrade F, Bilyy R, Chatfield S, Cichon I, Clancy DM, Desai J, Dumych T, Dwivedi N, Gordon RA, Hahn J, Hidalgo A, Hoffmann MH, Kaplan MJ, Knight JS, Kolaczkowska E, Kubes P, Leppkes M, Manfredi AA, Martin SJ, Maueröder C, Maugeri N, Mitroulis I, Munoz LE, Nakazawa D, Neeli I, Nizet V, Pieterse E, Radic MZ, et al. To NET or not to NET: current opinions and state of the science regarding the formation of neutrophil extracellular traps. Cell Death Differ, 26, 395-408, 2019.
  2. Dwivedi, N, Radic, M. Burning controversies in NETs and autoimmunity: The mysteries of cell death and autoimmune disease. Autoimmunity, 51 (6), 267-280, 2018.
  3. Hollingsworth, TJ, Radic, MZ, Beranova-Giorgianni, S, Giorgianni, F, Wang, Y, Iannaccone, A. Murine Retinal Citrullination Declines With Age and is Mainly Dependent on Peptidyl Arginine Deiminase 4 (PAD4). Invest Ophthalmol Vis Sci, 59 (10), 3808-3815, 2018.
  4. Allison E. Fetz; Indira Neeli; Karyl K. Buddington; Robert W. Read; Matthew P. Smeltzer; Marko Z. Radic; Gary L. Bowlin. Localized Delivery of Cl-Amidine From Electrospun Polydioxanone Templates to Regulate Acute Neutrophil NETosis: A Preliminary Evaluation of the PAD4 Inhibitor for Tissue Engineering. Frontiers in Pharmacology, 9, 2018.
  5. Mykolas Bendorius; Indira Neeli; Fengjuan Wang; Srinivasa Reddy Bonam; Eszter Dombi; Nelly Buron; Annie Borgne-Sanchez; Joanna Poulton; Marko Radic; Sylviane Muller. The Mitochondrion-lysosome Axis in Adaptive and Innate Immunity: Effect of Lupus Regulator Peptide P140 on Mitochondria Autophagy and NETosis. Frontiers in Immunology, 9, 2018.
  6. Marko Radic; Debendra Pattanaik. Cellular and Molecular Mechanisms of Anti-Phospholipid Syndrome. Frontiers in Immunology, 9, 2018.
  7. Selders, GS, Fetz, AE, Radic, MZ, Bowlin, GL. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen Biomater, 4 (1), 55-68, 2017.
  8. Dwivedi, N, Hedberg, A, Zheng, YY, Neeli, I, Satoh, M, Morel, L, Rekvig, OP, Radic, M. B Cell Tolerance to Deiminated Histones in BALB/c, C57BL/6, and Autoimmune-Prone Mouse Strains. Front Immunol, 8, 362, 2016.
  9. Neeli, I, Radic, M. Current Challenges and Limitations in Antibody-Based Detection of Citrullinated Histones. Front Immunol, 7, 528, 2016.
  10. Muller, S, Radic, M. Oxidation and mitochondrial origin of NET DNA in the pathogenesis of lupus. Nat Med, 22 (2), 126-7, 2016.
  11. Muller, S, Radic, M. Citrullinated Autoantigens: From Diagnostic Markers to Pathogenetic Mechanisms. Clin Rev Allergy Immunol, 49 (2), 232-9, 2015.
  12. Iannaccone, A, Giorgianni, F, New, DD, Hollingsworth, TJ, Umfress, A, Alhatem, AH, Neeli, I, Lenchik, NI, Jennings, BJ, Calzada, JI, Satterfield, S, Mathews, D, Diaz, RI, Harris, T, Johnson, KC, Charles, S, Kritchevsky, SB, Gerling, IC, Beranova-Giorgianni, S, Radic, MZ, ,. Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis. PLoS One, 10 (12), e0145323, 2015.
  13. Dwivedi, N, Neeli, I, Schall, N, Wan, H, Desiderio, DM, Csernok, E, Thompson, PR, Dali, H, Briand, JP, Muller, S, Radic, M. Deimination of linker histones links neutrophil extracellular trap release with autoantibodies in systemic autoimmunity. FASEB J, 28 (7), 2840-51, 2014.
  14. Radic, M. Clearance of Apoptotic Bodies, NETs, and Biofilm DNA: Implications for Autoimmunity. Front Immunol, 5, 365, 2014.
  15. Radic, M, Weigert, MG, Khan, SN, Han, J, Kalinina, O, Luning Prak, ET. Antibodies that bind complex glycosaminoglycans accumulate in the Golgi. Proc Natl Acad Sci U S A, 110 (29), 11958-63, 2013.
  16. Radic, M, Kaplan, MJ. Extracellular chromatin traps interconnect cell biology, microbiology, and immunology. Front Immunol, 4, 160, 2013.
  17. Radic, M, Herrmann, M, van der Vlag, J, Rekvig, OP. Regulatory and pathogenetic mechanisms of autoantibodies in SLE. Autoimmunity, 44 (5), 349-56, 2011.
  18. Khan, SN, Cox, JV, Nishimoto, SK, Chen, C, Fritzler, MJ, Hendershot, LM, Weigert, M, Radic, M. Intra-Golgi Formation of IgM-Glycosaminoglycan Complexes Promotes Ig Deposition. J Immunol, 2011.
  19. Neeli, I, Dwivedi, N, Khan, S, Radic, M. Regulation of extracellular chromatin release from neutrophils. J Innate Immun, 1 (3), 194-201, 2009.
  20. Radic, M. Tracking and trapping somatic mutations in Ig genes. J Immunol, 180 (9), 5763-4, 2008.
  21. Kiefer, K, Nakajima, PB, Oshinsky, J, Seeholzer, SH, Radic, M, Bosma, GC, Bosma, MJ. Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM. J Immunol, 180 (9), 6094-106, 2008.
  22. Khan, SN, Witsch, EJ, Goodman, NG, Panigrahi, AK, Chen, C, Jiang, Y, Cline, AM, Erikson, J, Weigert, M, Prak, ET, Radic, M. Editing and escape from editing in anti-DNA B cells. Proc Natl Acad Sci U S A, 105 (10), 3861-6, 2008.
  23. Neeli, I, Khan, SN, Radic, M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol, 180 (3), 1895-902, 2008.
  24. Neeli, I, Richardson, MM, Khan, SN, Nicolo, D, Monestier, M, Radic, MZ. Divergent members of a single autoreactive B cell clone retain specificity for apoptotic blebs. Mol Immunol, 44 (8), 1914-21, 2007.
  25. Radic, MZ, Shah, K, Zhang, W, Lu, Q, Lemke, G, Hilliard, GM. Heterogeneous nuclear ribonucleoprotein P2 is an autoantibody target in mice deficient for Mer, Axl, and Tyro3 receptor tyrosine kinases. J Immunol, 176 (1), 68-74, 2006.
  26. Bosma, GC, Oshinsky, J, Kiefer, K, Nakajima, PB, Charan, D, Congelton, C, Radic, M, Bosma, MJ. Development of functional B cells in a line of SCID mice with transgenes coding for anti-double-stranded DNA antibody. J Immunol, 176 (2), 889-98, 2006.
  27. Cline, AM, Radic, MZ. Apoptosis, subcellular particles, and autoimmunity. Clin Immunol, 112 (2), 175-82, 2004.
  28. Radic, M, Marion, T, Monestier, M. Nucleosomes are exposed at the cell surface in apoptosis. J Immunol, 172 (11), 6692-700, 2004.
  29. Brady, GF, Congdon, KL, Clark, AG, Sackey, FN, Rudolph, EH, Radic, MZ, Foster, MH. Kappa editing rescues autoreactive B cells destined for deletion in mice transgenic for a dual specific anti-laminin Ig. J Immunol, 172 (9), 5313-21, 2004.
  30. Radic, MZ, Weigert, M. Intricacies of anti-DNA autoantibodies. J Immunol, 172 (6), 3367; author reply 3367-8, 2004.
  31. Cline, AM, Radic, MZ. Murine lupus autoantibodies identify distinct subsets of apoptotic bodies. Autoimmunity, 37 (2), 85-93, 2004.
  32. Li, H, Jiang, Y, Cao, H, Radic, M, Prak, EL, Weigert, M. Regulation of anti-phosphatidylserine antibodies. Immunity, 18 (2), 185-92, 2003.
  33. Bosma, GC, Kim, J, Urich, T, Fath, DM, Cotticelli, MG, Ruetsch, NR, Radic, MZ, Bosma, MJ. DNA-dependent protein kinase activity is not required for immunoglobulin class switching. J Exp Med, 196 (11), 1483-95, 2002.
  34. Cocca, BA, Cline, AM, Radic, MZ. Blebs and apoptotic bodies are B cell autoantigens. J Immunol, 169 (1), 159-66, 2002.
  35. Li, H, Jiang, Y, Prak, EL, Radic, M, Weigert, M. Editors and editing of anti-DNA receptors. Immunity, 15 (6), 947-57, 2001.
  36. Cocca, BA, Seal, SN, D'Agnillo, P, Mueller, YM, Katsikis, PD, Rauch, J, Weigert, M, Radic, MZ. Structural basis for autoantibody recognition of phosphatidylserine-beta 2 glycoprotein I and apoptotic cells. Proc Natl Acad Sci U S A, 98 (24), 13826-31, 2001.
  37. Seal, SN, Monestier, M, Radic, MZ. Diverse roles for the third complementarity determining region of the heavy chain (H3) in the binding of immunoglobulin Fv fragments to DNA, nucleosomes and cardiolipin. Eur J Immunol, 30 (12), 3432-40, 2000.
  38. Seal, SN, Hoet, RM, Raats, JM, Radic, MZ. Analysis of autoimmune bone marrow by antibody-phage display: somatic mutations and third complementarity-determining region arginines in anti-DNA gamma and kappa V genes. Arthritis Rheum, 43 (9), 2132-8, 2000.
  39. Chen, ZC, Radic, MZ, Galili, U. Genes coding evolutionary novel anti-carbohydrate antibodies: studies on anti-Gal production in alpha 1,3galactosyltransferase knock out mice. Mol Immunol, 37 (8), 455-66, 2000.
  40. Cocca, BA, Seal, SN, Radic, MZ. Tandem affinity tags for the purification of bivalent anti-DNA single-chain Fv expressed in Escherichia coli. Protein Expr Purif, 17 (2), 290-8, 1999.
  41. Galili, U, Wang, L, LaTemple, DC, Radic, MZ. The natural anti-Gal antibody. Subcell Biochem, 32, 79-106, 1999.
  42. Radic, MZ, Cocca, BA, Seal, SN. Initiation of systemic autoimmunity and sequence specific anti-DNA autoantibodies. Crit Rev Immunol, 19 (2), 117-26, 1999.
  43. Galili, U, LaTemple, DC, Radic, MZ. A sensitive assay for measuring alpha-Gal epitope expression on cells by a monoclonal anti-Gal antibody. Transplantation, 65 (8), 1129-32, 1998.
  44. Wang, L, Radic, MZ, Siegel, D, Chang, T, Bracy, J, Galili, U. Cloning of anti-Gal Fabs from combinatorial phage display libraries: structural analysis and comparison of Fab expression in pComb3H and pComb8 phage. Mol Immunol, 34 (8-9), 609-18, 1997.
  45. Radic, MZ, Seal, SN. Selection of recurrent V genes and somatic mutations in autoantibodies to DNA. Methods, 11 (1), 20-6, 1997.
  46. Radic, MZ, Zouali, M. Receptor editing, immune diversification, and self-tolerance. Immunity, 5 (6), 505-11, 1996.
  47. Monestier, M, Kandiah, DA, Kouts, S, Novick, KE, Ong, GL, Radic, MZ, Krilis, SA. Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. J Immunol, 156 (7), 2631-41, 1996.
  48. Radic, MZ, Weigert, M. Origins of anti-DNA antibodies and their implications for B-cell tolerance. Ann N Y Acad Sci, 764, 384-96, 1995.
  49. Ibrahim, SM, Weigert, M, Basu, C, Erikson, J, Radic, MZ. Light chain contribution to specificity in anti-DNA antibodies. J Immunol, 155 (6), 3223-33, 1995.
  50. Radic, MZ, Ibrahim, SM, Rauch, J, Camper, SA, Weigert, M. Constitutive secretion of transgene-encoded IgG2b autoantibodies leads to symptoms of autoimmune disease. J Immunol, 155 (6), 3213-22, 1995.
  51. Wang, L, Radic, MZ, Galili, U. Human anti-Gal heavy chain genes. Preferential use of VH3 and the presence of somatic mutations. J Immunol, 155 (3), 1276-85, 1995.
  52. Chen, C, Nagy, Z, Radic, MZ, Hardy, RR, Huszar, D, Camper, SA, Weigert, M. The site and stage of anti-DNA B-cell deletion. Nature, 373 (6511), 252-5, 1995.
  53. Chen, C, Radic, MZ, Erikson, J, Camper, SA, Litwin, S, Hardy, RR, Weigert, M. Deletion and editing of B cells that express antibodies to DNA. J Immunol, 152 (4), 1970-82, 1994.
  54. Radic, MZ, Weigert, M. Genetic and structural evidence for antigen selection of anti-DNA antibodies. Annu Rev Immunol, 12, 487-520, 1994.
  55. Galili, U, Anaraki, F, Thall, A, Hill-Black, C, Radic, M. One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody. Blood, 82 (8), 2485-93, 1993.
  56. Radic, MZ, Mackle, J, Erikson, J, Mol, C, Anderson, WF, Weigert, M. Residues that mediate DNA binding of autoimmune antibodies. J Immunol, 150 (11), 4966-77, 1993.
  57. Radic, MZ, Erikson, J, Litwin, S, Weigert, M. B lymphocytes may escape tolerance by revising their antigen receptors. J Exp Med, 177 (4), 1165-73, 1993.
  58. Radic, MZ, Saghbini, M, Elton, TS, Reeves, R, Hamkalo, BA. Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete for binding to mouse satellite DNA. Chromosoma, 101 (10), 602-8, 1992.
  59. Yui, K, Bhandoola, A, Radic, MZ, Komori, S, Katsumata, M, Greene, MI. Inhibition of abnormal T cell development and autoimmunity in gld mice by transgenic T cell receptor beta chain. Eur J Immunol, 22 (7), 1693-700, 1992.
  60. Radic, MZ, Mascelli, MA, Erikson, J, Shan, H, Weigert, M. Ig H and L chain contributions to autoimmune specificities. J Immunol, 146 (1), 176-82, 1991.
  61. Erikson, J, Radic, MZ, Camper, SA, Hardy, RR, Carmack, C, Weigert, M. Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice. Nature, 349 (6307), 331-4, 1991.
  62. Shlomchik, M, Mascelli, M, Shan, H, Radic, MZ, Pisetsky, D, Marshak-Rothstein, A, Weigert, M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med, 171 (1), 265-92, 1990.
  63. Radic, MZ, Mascelli, MA, Erikson, J, Shan, H, Shlomchik, M, Weigert, M. Structural patterns in anti-DNA antibodies from MRL/lpr mice. Cold Spring Harb Symp Quant Biol, 54 Pt 2, 933-46, 1989.
  64. Radic, MZ, Lundgren, K, Hamkalo, BA. Curvature of mouse satellite DNA and condensation of heterochromatin. Cell, 50 (7), 1101-8, 1987.