Prior Funding

Elucidating the molecular basis of the impaired immune regulation that results in
autoimmune disease remains one of the most significant challenges in all of
medicine. Increased expression of interferon-alpha is a feature of most patients
with systemic lupus erythematosus (SLE), and the consequences of interferon
pathway activation include multiple effects on immune system function that
lead to autoimmunity, inflammation and tissue damage. Small RNA molecules
called microRNAs represent one class of regulatory molecules that could
contribute to activation of the interferon pathway and autoimmunity. We found
that human microRNA-31 (miR-31) is relatively depressed in lupus patients
compared to healthy subjects. Detailed investigation of the mechanisms by
which low levels of miR-31 might impact immune function revealed miRNA
targets in the type I interferon signaling system. We are currently using a
combination of molecular cell biology approaches to define in detail the targets
of miR-31 relevant to the interferon pathway. Our long-term goal is to
understand how the interferon system in SLE is activated and thereby identify
novel therapeutic targets for the treatment of the disease.