microRNAs in Systemic Lupus Erythematosus
RNA interference (RNAi) operates as a mechanism of innate immunity in plants, drosophila and C. elegans and depends on double stranded RNA and proteins of the Argonaute family. RNAi, programmed by exogenous small RNAs, is a powerful tool for gene-specific studies. The microRNA pathway intersects with the RNAi pathway and regulates gene expression in plants and animals. Animal microRNAs bind directly to Argonaute proteins (Ago1-4), providing target specificity to the regulatory function of Ago complexes. Research in the Kiriakidou lab focused on the biology of animal Ago proteins by studying the expression, regulation and function of animal Agos in human and mouse cells, mouse models and in vitro systems.
MicroRNAs are involved in numerous biological processes, and their expression is differentially regulated in human disease. Systemic Lupus Erythematosus (SLE, lupus) is a prototype systemic autoimmune disease characterized by autoantibody production and tissue deposition of immune complexes. Immunopathology in lupus is characterized by aberrant B and T cell functions. We are studying the role of microRNAs in pathways contributing to disease-specific B and T cell phenotypes and organ damage in SLE using microRNA KO models and mouse lupus models (congenic and induced). We also use synthetic inhibitors for microRNA silencing in vivo, to complement our genetic studies and to investigate potential use of microRNA.
Barry Garchow, PhD