Instructor of Medicine
M.D.:
Internship and Residency:
Post-doctoral Fellowship: Johns Hopkins University, Rheumatology
The autoantibody response in systemic lupus erythematosus (SLE) targets antigens that are ubiquitously expressed. However, the mechanisms underlying antigen selection and propagation of the immune response remain poorly defined. Recent evidence suggests that abnormalities during apoptosis, including defective clearance of apoptotic cells and antigen modification, may play an important role for the development of immunogenicity.
The main focus of my project is to study the role of antigen processing during apoptosis in an inducible mouse model of SLE, the parent-into-F1 chronic GVHD (cGVHD) model. In a first step, we have identified prevalent autoantigens in this model that are processed during apoptosis. One of the major antigen targets is poly(ADP-ribose) polymerase 1 (PARP-1). a DNA repair enzyme that is extensively modified during apoptosis by cleavage through caspases and granzymes. By using gene-deficient mouse strains and pharmacologic inhibitors we are now defining key components of the apoptotic pathway responsible for the induction of the immune response. In collaboration with Michelle Petri, who directs the SLE cohort at Hopkins, we are studying the relevance of our results from the cGVHD model for human SLE. In initial experiments we have determined that PARP-1 is a prevalent autoantigen in human SLE and that the presence of serum antibodies to modified PARP-1 may identify patients with active disease.
My long-term goal is to establish a laboratory with focus on translational research in systemic autoimmunity.
