Telomere Biology and Telomere Disease
Our studies focus on understanding how telomere dysfunction causes human diseases, including cancer, dyskeratosis congenita, and idiopathic pulmonary fibrosis. Telomere is the molecular clock of cellular ageing. It is a protective structure at the end of chromosomes, which can prevent chromosomal recombination and fusion and maintain the stability of the genome. However, DNA replication in somatic cells gradually shortens telomeres, resulting in loss of telomere dysfunction, causing cell growth and aging, but from the perspective of cancer generation, this is an important cancer suppression mechanism. Therefore, the maintenance of telomeres is directly linked to the generation of rare diseases of aging and cancer. We use cell and mouse models to explore how the telomere defects in the process of disease formation induce cellular response, which in turn affects the normal function of cells and tissues. Recently, we have found that loss of telomere function can induce innate immune response and regulate the formation of cancer, especially in childhood brain tumors and bone cancer. On the other hand, we have also found that innate immune response triggers cellular aging. Through the understanding of disease mechanisms, we look forward to identifying strategies for the treatment of telomere-related diseases and developing treatment methods.
Main directions of our research:
(1) Free telomere DNA activates the innate immune response and regulates cancer development.
(2) Telomere defects activate the innate immune response and promote aging diseases.
(3) Structural changes of telomeres in diseases.
- PDF, 2009-2013, École Polytechnique Fèdèrale de Lausanne, Switzerland
- Ph.D., 2009, Dept. of Biochem. & Mol. Biol., Baylor College of Medicine, USA
- MS, 1999, Dept. of Life Sciences, National Tsing-Hua University
- BS, 1977, Dept. of Chemistry, National Tsing-Hua University
- 2016-2020, Academia Sinica Career Development Award
- 2019, Academia Sinica Early-Career Investigator Research Achievement Award
- Chen, L.-Y., Zhang, Y., Li, H., Zhang, Q., Fang, H., Yotnda, P., Kim, S-H., Qin, L., Xu, J., Tu, B., Bai, Y., Sonagyang, Z. (2012) Mitochondrial Localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol. Cell 47: 839-850.
- Chen, L.-Y., Redon, S., Lingner, J. (2012) The human CST complex is a terminator of telomerase activity. Nature 488: 540-544.
- Chen, Y.-A., Shen, Y.-L., Hsia, H.-Y., Tiang, Y.-P., Sung, T.-L., Chen, L.-Y. (2017) Extrachromosomal telomere repeat DNA is linked to ALT development via cGASSTING DNA sensing pathway. Nat. Struct. Mol. Biol. 24(12): 1124-31.
- Khoo, L.-T., Chen, L.-Y. (2018) Role of the cGASSTING pathway in cancer development and potential as a cancer therapeutic target. EMBO Reports 19(12): e46935.
- Chen, C.-F., Sung, T.-L., Chen, L.-Y., Chen, J.-H. (2018) Telomere maintenance during anterior regeneration and aging in fresh water annelid Aeolosoma viride. Scientific Reports 8(1): 18078.
- Chen, R.-L., Lin, K.-K., Chen, L.-Y. (2019) Complications for a Hoyeraal-Hreidarsson syndrome patient with a germline DKC1 A353V variant undergoing unrelated peripheral blood stem cell transplantation. Int. J. Mol. Sci. 20(13): 3261.
