From atomic resolution to systems level investigation of chromosome ends Telomeres, the nucleoprotein complexes at the ends of chromosomes, shell chromosome ends and maintain their complete replication. The loss of telomere protection/maintenance is the cause of the premature aging symptoms associated with Dyskeratosis congenita and other telomeropathies. Telomere dysfunction also plays an important role in the early stages of tumorigenesis and the activation of a telomere maintenance system. It is a hallmark of human cancer. We study telomere nucleoprotein complexes and telomerase RNA-protein enzyme from various aspects, including their atomic resolution structures, epigenetic regulations, and interactions with other pathways. The long-term goal of our research program is to achieve a comprehensive understanding of the fundamental mechanisms that control telomere length homeostasis from the atomic to the systems level. Since telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions, our research naturally extends to identifying small molecular drugs targeting telomere proteins to cure cancer and age-dependent disorders.
Long non-coding RNA (lncRNA) structure, biogenesis and functions Our initial interests in lncRNA stems from telomerase RNA, one of the few lncRNAs that are functionally well-defined. We are expanding our investigations to the roles of biogenesis factors, RNA structure folding factors (we discovered in telomerase RNA production and telomerase RNP assembly) to other non-coding RNAs. We are particularly interested in lncRNAs associated with cancer.