STUDIES

Systemic Lupus Erythematosis (SLE)

The Baccala Group

Dr. Baccala’s research focuses on mechanisms of immunopathology in autoimmune and anti-viral responses, with an emphasis on two main areas. The first addresses the primary role of the innate immune system in systemic autoimmunity. The lab’s work in experimental models of lupus provide direct evidence for the essential role of type 1 interferons, endolysosomal Toll-like receptors (TLR), and plasmacytoid dendritic cells in disease pathogenesis, thereby contributing to the current paradigm that abnormal activation of this innate immune pathway by self-nucleic acids is a key event in systemic autoimmunity. The Baccala lab has also shown that the pathogenicity of this pathway can be controlled at the endolysosomal surface by modulating the function of SLC15A4, a peptide/histidine transporter and a promising new target. Current efforts aim at elucidating the mechanism by which SLC15A4 promotes TLR responses and developing specific pharmacologic inhibitors.

In addition, the Baccala lab investigates the contribution of microenvironment triggers of innate immune activation in systemic autoimmunity. They found that certain viral and xenobiotic agents, particularly when acting in combination, can significantly increase the susceptibility to lupus-like disease. These results support a multi-hit model of autoimmunity in which the effect of genetic predisposition is enhanced by microenvironmental exposures. Ongoing studies are examining the mechanistic basis for the observed synergisms.