Shu-Man Fu, MD, PhD
Regulation of immune responses to chronically expressed autoantigens
Autoimmunity plays an important role in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA. The emphasis of the Fu laboratory is on the genetic and environmental factors important for these disorders. They continue to study their mouse SLE model (NZM2328). In this model, they have identified a genetic region on chromosome 1 controlling autoantibody production and nephritis. Intrachromosomal recombinants have been generated which contain smaller genetic regions amenable to further analyses. Thus, this laboratory is focused on the identification of the genes involved in the pathogenesis of SLE. In addition, autoantigens which are the target for nephritis in NZM2328.C57L/J.c4 are to be identified. The hypothesis that molecular mimicry initiates the initial autoimmune response, which diversifies to multiple autoantigens, resulting in end organ damage in suitable hosts is being tested. The role of MHC in this process in both mice and men is being investigated. In this regard, bacterial and viral agents sharing cross reactive T and B cell epitopes with human autoantigens are logical candidates for molecular mimics in this process. Their working hypothesis is that both innate and adaptive immunity play an important role in the pathogenesis of SLE. Understanding the interaction between these two pathways has implications in the generation of tumor specific immunity.
The research program interacts closely with Dr. Joe Sung, Dr. Michael Brown, and Dr. Shyr-Te Ju. The collaboration with Dr. Sung focuses on the nature of dendritic cells important to the initiation of autoimmune response. The interaction with Dr. Brown focuses on the role of CMV infection as a cause of salivary gland dysfunction. Significant collaboration has been initiated with Dr. Ju to determine the feasibility of using activation induced cell death as a means for controlling autoimmunity.