Regulatory non-coding RNAs and RNA-binding proteins (RBPs) are important research areas in gene regulation and RNA biology. Our laboratory is interested in the understanding of pathophysiological function and molecular mechanism of new non-coding RNAs (and RBPs) and new modes of gene regulation in cardiac system and cardiovascular disease. We recently discovered a new type of stress-responsive, protein-directed human RNA switch that regulates expression of vascular endothelial growth factor-A in human monocytic cells (Ray, PS, et al. Nature 2008 457: 915-919; Yao, P, et al. Plos Biology 2013 11: e1001635) and may play a role in cardiovascular disorders and cancers. Intriguingly, some of these RNA switches involve the interplay between microRNA and RNA-binding protein (Jafarifar, F, et al. EMBO Journal 2011 30: 1324-1334). We also identified a novel mRNA processing mechanism that expands human proteome at the posttranscriptional level and regulates gene expression (Yao, P, et al. Cell 2012 149: 88-100). Our current research interest includes: (1) Pathophysiological function and regulatory mechanism of microRNA (and other noncoding RNA) and RNA-binding proteins in cardiac system and cardiovascular disorders; (2) Riboswitch-like RNA switch mechanisms of gene regulation in mammalian system; (3) The role of translation machinery and translational control in cardiovascular system and identification of therapeutic targets for treatment of cardiovascular diseases (e.g., cardiac hypertrophy and heart failure). We employ various approaches and methods of biochemistry and biophysics, molecular and cellular biology, and genetic and surgical mouse models, to dissect the convergent and divergent regulatory pathways. The long-term objective of our laboratory is to identify novel RNA-based molecular mechanisms that control gene expression and conduct pathophysiological function in cardiac system, as well as to develop novel therapeutic approaches for the prevention or treatment of human cardiovascular diseases.
