How different types of cells in intact tissues regulate their mRNAs in physiologic and disease conditions remains largely unexplored. My research goal is to study mRNA regulation in both physiologic and disease scenarios with a special emphasis on 3-prime UTR-mediated regulation. Cells use 3-prime untranslated regions (3-prime UTRs) as dynamic platforms to regulate mRNA stability, localization and translational efficiency in response to outside stimuli by interacting with regulators such as microRNAs (miRNAs) and RNA-binding proteins (RBPs). Moreover, erroneous 3-prime UTR-mediated mRNA regulation is frequently involved in human disease. One important mechanism to generate mRNA isoforms with distinct 3-prime UTR sequences is through alternative polyadenylation (APA), which has been recently shown to play important roles in fundamental cellular processes including proliferation and differentiation, and also in human disease such as cancer, vascular thrombosis, and neurological disorders. During my postdoctoral studies, I developed new tools to generate APA maps and mRNA expression profiles from specific cell types in intact tissues. These tools provide an exciting opportunity to explore new biology that is not feasible with existing methods. Combining high-throughput sequencing, mouse genetics and molecular biology techniques, my laboratory will apply these tools to discover and to study important APA events in human biology and disease.
