申请人主要从事端粒与个体衰老的机制研究。创新性提出“端粒存在拓扑结构影响复制衰老”的新机制；发现端粒在染色体内部的新功能，拓展了复制衰老定义；运用该原理设计了端粒药筛平台，高通量筛选出两个药物影响细胞衰老。以第一/通讯作者发表在CELL、Nat Rev Genet 等杂志12篇，影响因子101分，他引率194次。被Faculty of 1000 Post Publication Peer Review评价为“有创意和端粒复制的新发现”；获冷泉港和AACR等国际会议奖励;申请2项专利。本项目将探索间隔性端粒重复序列(ITS)是染色体内脆性位点，TRF2等重要端粒组件同时保护端粒和ITS，防止基因组DNA损伤。TRF2在端粒和ITS的动态平衡可能导致长距离染色质互动和重组，改变染色质空间构象，修饰转录重编程，影响细胞衰老。这是对“复制衰老”理论的补充，为探索以端粒为靶点的延缓衰老治疗提供依据。

The applicant is engaged in the basic and clinical research on telomere and　telomerase, especially in the direction of the role of telomeres on aging and　cellular senescence. Her main achievement in this research field is the discovery　of the existence of topology in telomere structure. She demonstrated that TRF2　coupling with Apollo and Top IIa acts as a multi-enzyme components in the　regulation of telomere replication, and the equilibrium of the three proteins at　telomeres are crucial for the maintenance of telomere structure and function. She also discovered that TRF2 has extra-telomeric role in transcriptional regulation by binding to the interstitial telomeric sequence (ITS). She has also discovered two medical drugs that are involved in cellular senescence based on the cell model she constructed that can influence telomeric heterochromatin. These two drugs are found by performing a high throughput screening of 1120 medical drugs in the Prestwick medical libraries. All these results have been published in several international peer view journals, including CELL, Nat Rev Genet. She has applied for 2 national patents. The total SCI IF of all her publications is more than 150. The SCI IF of her first and corresponding publications is 101. Her paper has been sited 194 times by others..The ongoing project will further reveal that telomeric components link to the nature of cellular senescence. Telomeric components might mediate long-distance interaction between telomeres and non-telomere chromosomal loci. Telomere shortening or dysfunction will lead to the dissociation of telomere key component from telomeres and re-localize at the inner part of the chromosome, which will finally modify the cellular transcriptional reprogramming. Thus, the original results of this project will extend the concept of telomere dysfunction, and induce a more profound hypothesis that telomere dysfunction not only lead to DNA damage pathways, but also stimulate long-range chromatin modification and transcriptional reprogramming of gene transcription. This study will provide innovative view for exploring telomere-based biomedical treatment of longevity and tissue degenerative diseases.