Molecular Physiology & Biophysics

Extracellular microRNAs have been identified in plasma, and our laboratory has identified these extracellular microRNAs are carried by lipoproteins including high-density lipoprotein (HDL). The goal of our laboratory is to characterize the role of these extracellular microRNAs, particularly to elucidate whether extracellular microRNAs may function as a novel cell-to-cell communication pathway. Within cells, microRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Specifically, I study the myeloid-derived microRNA, miR-223, to understand to what tissue and cell types receive microRNA-223 after being exported from myeloid cells. To do this, I utilize bone marrow transplants between wild-type and miR-223 knockout mice to restore or deplete the myeloid (miR-223 donor cell) population. After restoring or depleting the myeloid population (miR-223 donor cell) I examine variety of tissue types and pure cell isolations to map out the delivery of extracellular miR-223 in vivo. My second project focuses on the role of endothelial microRNAs in the progression of Chronic Kidney Disease-associated atherosclerosis. I have found that complexing two microRNA inhibitors to HDL, allows me to effectively reduce endothelial microRNA levels. The decreased microRNA levels result in a dramatic reduction in atherosclerosis in vivo, which may be mediated through altered FAM220a regulation of STAT3 activation causing less inflammation.