Long non-coding RNAs in the immune system

Our lab is interested in understanding how gene expression is regulated during the host response to infection. Ligation of TLRs and other sensors trigger intracellular signaling cascades that converge on well-defined transcription factors leading to rapid, dynamic and temporally regulated changes in transcription of hundreds of genes involved in antimicrobial defense. While much of our earlier work in this area focused on signaling pathways that converge on NF-kappaB and interferon regulatory factors, we have more recently uncovered a new layer of regulation in immune cells mediated by long non-coding RNAs (lncRNAs). lncRNAs are noncoding RNAs that have at least 200 nucleotides and typically regulate transcription of other genes through their interactions with chromatin modifiers and RNA binding proteins. We have identified large numbers of lncRNAs that are expressed in macrophages and dendritic cells and differentially regulated during immune cell differentiation and activation. In both published and ongoing studies we are systematically characterizing the role of these lincRNAs in controlling macrophage and dendritic cell function. We accomplish these goals using biochemical, molecular, and genetic (KO) approaches. Ultimately we aim to uncover new layers of regulation of inflammation that could unveil new targets for the treatment of inflammatory diseases.