Marko Radic, Ph.D.
858 Madison Ave.
Room 201 Molecular Science Building
Memphis, TN 38163
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. People 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 apoptotic cells. Several lines of evidence, including genetic studies in mice and humans, suggest that apoptotic cells are the main suppliers of autoantigens. When clearance of apoptotic cells is slow or inefficient, dying cells release autoantigens, thus inducing autoimmunity. The Radic lab has demonstrated this principle for autoantibodies to nuclear antigens composed of DNA and histones (i.e. the nucleosome core particle), RNA and RNA-binding proteins, as well as to phosphatidylserine, a phospholipid exposed on the surface of apoptotic cells. 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. This result provides a link between innate immunity to infection and the covalent modification of histones.
Our results are relevant for the understanding of the induction 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 findings will find applications in the therapy of autoimmune disease.
- 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