Ansar Ahmed, PhD, DVM, Virginia Tech

"Are microRNA, Novel Regulators in Immunity, Involved in Autoimmune Lupus?"

2008 Novel Pilot Projects Program

This grant award is presented in memory of Kassie McMullin Biglow

A major, exciting finding in gene regulation is the recent identification of small ribonucleic acids, called microRNA (miRNA). Already, their biomedical impact in tumorigenesis, development, and cell function has been reported. Further, the role of miRNA in homeostasis of the immune system has been reported, which proposes an entirely new paradigm of regulation of immunity. Our recent studies have shown that estrogen, a promoter of autoimmune lupus, regulates the expression of miRNA in spleen cells of normal (non autoimmune) C57BL/6 mice. To date, studies on dysregulated miRNA in autoimmune states are very limited. Therefore, the goal of the proposed studies is to investigate the role of miRNA in the pathogenesis of systemic lupus erythematosus (SLE) using autoimmune prone NZB/W mice, a well-tested, classical model of human lupus. Given the role of miRNA in immune regulation, the hypothesis that aberrant expression of miRNA may occur in autoimmune states such as in autoimmune lupus is plausible. We will identify signature miRNA expressed in spleen cells from NZB/W mice during active disease states. Further, we anticipate that manipulation of lupus related miRNA activity in spleen cells from mice with active disease will ameliorate production of autoantibodies, as well as inflammatory cytokines. Our studies may provide unique, novel, molecular diagnostic markers for lupus, and offer entirely new therapeutic approaches, such as manipulation of lupus-related miRNA, to correct pathological conditions.