MicroRNA-155 regulation of disease-associated inflammatory responses
MicroRNA-155 has emerged as a multi-faceted regulator of mammalian immune responses that is expressed by a variety of activated immune cells and that targets a wide range of relevant target genes. We are investigating miR-155’s role in the pathogenesis of Multiple Sclerosis, regulation of tumor immunity, promotion of inflammatory hematopoiesis, and modulation of antibody mediated immunity.
MicroRNA coordination of host-commensal bacteria interactions
The mammalian intestines contain a complex community of commensal microbes, while approximately 75% of mammalian immune cells also reside within intestinal tissues. Thus, significant host-commensal interactions occur within the gut, and these are proving to have profound impacts on host health and disease. We are exploring how specific microRNAs regulate the host response to commensal bacteria, and how this dictates microbial community composition, host tissue penetration and disease phenotypes such as inflammatory bowel disease and colorectal cancer.
The molecular mechanisms and biology of extracellular microRNAs
Although microRNAs clearly function in the cytoplasm of the cells where they are transcribed, recent data indicate that microRNAs are also secreted from cells and taken up by recipient cells. Thus, certain microRNAs also appear to act in a paracrine or endocrine manner to transfer information between cells. We are studying the mechanisms by which microRNAs are selectively loaded into vesicles that are released from inflammatory immune cells, and determining the functional relevance of exosomal microRNA uptake by recipient cells.
Discovery of novel noncoding RNAs that regulate inflammatory responses
Although most of the human genome is transcribed, only about 1% of RNA transcripts encode proteins. Thus, most of the transcriptome is comprised of noncoding RNAs that likely play important regulatory roles during inflammatory responses. We are taking a variety of approaches to identify and study novel noncoding RNAs that function to coordinate mammalian immunity.