Marko Radic, Ph.D.


Marko Radic, Ph.D.

Associate Professor
858 Madison Ave.
Room 201 Molecular Science Building
Memphis, TN 38163
Email: mradic@uthsc.edu
Phone: 901-448-8219
Fax: 901-448-7360

 

Research Interests

Work in the Radic laboratory centers on the mechanisms leading to autoimmune disease, with an emphasis on disorders that are diagnosed and mediated by autoantibodies. The lab has made contributions toward understanding molecular mechanisms of Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Anti-Phospholipid Syndrome (APS), Felty's Syndrome (FS), and Sjogren's Syndrome (SS). 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 to test hypotheses that account for mechanisms of antigen selection. For this purpose, autoantibodies are expressed from hybridoma cell lines, or as recombinant antibody fragments in heterologous systems. Researchers in the Radic lab examine the binding specificities of autoantibodies, in order to determine likely stimuli for the induction of autoimmune responses.

Recent experiments have focused on autoantibody binding to nuclear autoantigens. Discoveries made in the Radic lab include the regulation of histone deimination, a post-translational modification of a major nuclear autoantigen. Deimination converts arginine residues in histone N-termini to citrulline residues (Figure 1), a reaction that is induced by inflammatory stimuli acting on neutrophil granulocytes.


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The deimination reaction is carried out by peptidylarginine deiminase 4 (PAD4) and forms part of a coordinated set of enzymatic reactions that are required for a unique type of neutrophil cell death called NETosis (Figure 2).


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NETosis is notable for the release of nuclear chromatin from the cell, a circumstance that leads to the extracellular exposure of DNA and histones (Figure 3). Such extracellular chromatin could interact with the immune system and stimulate the production of autoantibodies.


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In support of this scenario, the Radic lab has identified human autoantibodies with preferential binding to deiminated histones. Work over the last several years provides a link between innate immunity to infection, the covalent modification of histones, and the induction of an important category of human autoantibodies.

Our results are relevant for the understanding of the initial stages of autoimmunity, a process that is still mysterious. We hope that our discoveries will be useful in designing and testing methods for inhibiting the ill effects of autoantibodies in pathogenesis and that our insights will contribute to new therapies for autoimmune diseases.

 

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Education

  • Ph.D. in Molecular Biology and Biochemistry at the University of California in Irvine
  • B. S. in Genetics at the University of California in Davis

Dr. Marko Radic CV