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姓名:李宜靜

職稱:助研究員

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專長:Genetics,
Cellular and Molecular Biology

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2013.8-

Assistant Research Fellow, Institute of Cellular and Organismic Biology, Academia Sinica, Taiwan

 

2011.8-2013.7

Assistant Professor, Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan

 

2009.8-2011.7,

Adjunct Assistant Professor, Institute of Integrated Medicine, China Medial University, Taichung, Taiwan

 

2006.11-2011.7,

Postdoctoral Research Fellow and Group leader, National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

 

2003.3-2006.8,

Visiting Fellow, National Institute of Child Health& Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD.

 

2003.1,

Ph.D., Graduate Institute of Life Science, National Defense University, Taipei, Taiwan.

 

李宜靜老師實驗室

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    Our lab studies the molecular basis of several genetic diseases with the aim to apply this knowledge to development of rational therapeutic approaches for these diseases. The specific projects at present time include:
     
     
    1.Functional characterization of a novel glucose transporter (GLUT10) and its role in arterial tortuosity syndrome (ATS) and type 2 diabetes mellitus (T2D). GLUT10, a member of the glucose transporter family, has been implicated in type 2 diabetes. Studies have found that loss-of-function GLUT10 mutations in humans lead to a Mendelian recessive disorder, ATS, a connective tissue disorder. However, the physiological function of GLUT10 and how might the gene mutations lead to the disease remain unclear. We have established that GLUT10 locates in the mitochondria of aortic smooth muscle cells and insulin stimulated adipocytes and further demonstrated that GLUT10 facilitates transport of dehydroascorbic acid, the oxidize form of ascorbic acid, and protects cells from oxidative stress. These results suggest that GLUT10 plays a critical role in ascorbic acid and redox homeostasis. Furthermore, our preliminary results suggest a new transport route to mitochondria of GLUT10. We have established mouse models with different levels of GLUT10 deficiency. We are investigating the intracellular transport pathway of GLUT10 and the roles of GLUT10 in ATS and T2D.
     
    2.Treatment Strategies for Skeletal Dysplasias and Cancers. The activating mutations of Fibroblast growth factor receptor 3 (FGFR3) are known to cause skeletal dysplasias and be associated with certain human cancers. We have established a high throughput cell-based translocation assay system for natural complex compounds screening. We have identified several plant extracts and the ability to inhibit the growth of FGFR3 activating multiple myeloma cells was validated. We generated an achondroplasia mouse model carrying human achondroplasia FGFR3 mutation. The in vivo functions for treatment of achondroplasia of these functional nature compounds will be further tested in the mouse model. 
     
    3.The disease pathogenesis of Kawasaki disease (KD). Kawasaki disease (KD) is an acute, self-limited vasculitis predominantly affecting infants and young children. Coronary artery aneurysms develop in 15–25% of untreated patients making KD the leading cause of acquired heart disease in children in developed countries. However, no pathogen has been isolated, and the aetiology of KD remains unknown. Several candidates associated with KD involved in immune and inflammation pathways have been identified in Han Chinese resident in Taiwan by genome wild association studies. These results have been further validated in other ethnicity cohorts. The causative SNP identification and further functional studies will be performed.
     








     
     
     
     
     



     

     

     

  • 姓名職稱電話Email備註
    李宜靜助研究員
    許育維研究助理
    江忠霖研究助理
    前實驗室成員
    賴浩文碩士班學生
    陳妍如暑期大專生
    江欣璉碩士班學生
    黃鈺婷碩士班學生
    黃晴瑜碩士班學生
    1. Lee, Y. C.*, Song, I. W., Pai, Y. J., Chen, S. D., and Chen, Y. T. (2017) Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia. Scientific reports 7, 43220 (* corresponding authors)
    2. Lenka, G., Tsai, M. H., Lin, H. C., Hsiao, J. H., Lee, Y. C., Lu, T. P., Lee, J. M., Hsu, C. P., Lai, L. C., and Chuang, E. Y. (2017) Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma. Scientific reports 7, 42573
    3. Ko, T. M., Kuo, H. C., Chang, J. S., Chen, S. P., Liu, Y. M., Chen, H. W., Tsai, F. J., Lee, Y. C., Chen, C. H., Wu, J. Y., and Chen, Y. T. (2015) CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease. Circulation research 116, 876-883
    4. Lin, Y. C., Lee, Y. C., Li, L. H., Cheng, C. J., and Yang, R. B. (2014) Tumor suppressor SCUBE2 inhibits breast-cancer cell migration and invasion through the reversal of epithelial-mesenchymal transition. Journal of cell science 127, 85-100
    5. Chen, C. H., Lee, C. S., Lee, M. T., Ouyang, W. C., Chen, C. C., Chong, M. Y., Wu, J. Y., Tan, H. K., Lee, Y. C., Chuo, L. J., Chiu, N. Y., Tsang, H. Y., Chang, T. J., Lung, F. W., Chiu, C. H., Chang, C. H., Chen, Y. S., Hou, Y. M., Chen, C. C., Lai, T. J., Tung, C. L., Chen, C. Y., Lane, H. Y., Su, T. P., Feng, J., Lin, J. J., Chang, C. J., Teng, P. R., Liu, C. Y., Chen, C. K., Liu, I. C., Chen, J. J., Lu, T., Fan, C. C., Wu, C. K., Li, C. F., Wang, K. H., Wu, L. S., Peng, H. L., Chang, C. P., Lu, L. S., Chen, Y. T., Cheng, A. T., and Taiwan Bipolar, C. (2014) Variant GADL1 and response to lithium therapy in bipolar I disorder. The New England journal of medicine 370, 119-128
    6. Chang, C. J., Kuo, H. C., Chang, J. S., Lee, J. K., Tsai, F. J., Khor, C. C., Chang, L. C., Chen, S. P., Ko, T. M., Liu, Y. M., Chen, Y. J., Hong, Y. M., Jang, G. Y., Hibberd, M. L., Kuijpers, T., Burgner, D., Levin, M., Burns, J. C., Davila, S., International Kawasaki Disease Genetics, C., Korean Kawasaki Disease Genetics, C., Taiwan Kawasaki Disease Genetics, C., Chen, Y. T., Chen, C. H., Wu, J. Y., and Lee, Y. C.* (2013) Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility. PLoS One 8, e72037 (* corresponding authors)
    7. Lee, Y. C., Kuo, H. C., Chang, J. S., Chang, L. Y., Huang, L. M., Chen, M. R., Liang, C. D., Chi, H., Huang, F. Y., Lee, M. L., Huang, Y. C., Hwang, B., Chiu, N. C., Hwang, K. P., Lee, P. C., Chang, L. C., Liu, Y. M., Chen, Y. J., Chen, C. H., Taiwan Pediatric, I. D. A., Chen, Y. T., Tsai, F. J., and Wu, J. Y. (2012) Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 44, 522-525
    8. Tsai, F. J.*, Lee, Y. C.*, Chang, J. S., Huang, L. M., Huang, F. Y., Chiu, N. C., Chen, M. R., Chi, H., Lee, Y. J., Chang, L. C., Liu, Y. M., Wang, H. H., Chen, C. H., Chen, Y. T., and Wu, J. Y. (2011) Identification of novel susceptibility Loci for kawasaki disease in a han chinese population by a genome-wide association study. PLoS One 6, e16853 (*, equal contribution)
    9. Lee, Y. C., Chang, C. J., Bali, D., Chen, Y. T., and Yan, Y. T. (2011) Glycogen-branching enzyme deficiency leads to abnormal cardiac development: novel insights into glycogen storage disease IV. Human molecular genetics 20, 455-465
    10. Khor, C. C.*, Davila, S.*, Breunis, W. B.*, Lee, Y. C., Shimizu, C., Wright, V. J., Yeung, R. S., Tan, D. E., Sim, K. S., Wang, J. J., Wong, T. Y., Pang, J., Mitchell, P., Cimaz, R., Dahdah, N., Cheung, Y. F., Huang, G. Y., Yang, W., Park, I. S., Lee, J. K., Wu, J. Y., Levin, M., Burns, J. C., Burgner, D., Kuijpers, T. W., and Hibberd, M. L. (2011) Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet 43, 1241-1246 (*, equal contribution)
    11. Cheng, P. Y., Lin, Y. P., Chen, Y. L., Lee, Y. C., Tai, C. C., Wang, Y. T., Chen, Y. J., Kao, C. F., and Yu, J. (2011) Interplay between SIN3A and STAT3 mediates chromatin conformational changes and GFAP expression during cellular differentiation. PLoS One 6, e22018
    12. Saha, A.*, Lee, Y. C.*, Zhang, Z., Chandra, G., Su, S. B., and Mukherjee, A. B. (2010) Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs. The Journal of biological chemistry 285, 10822-10831 (*, equal contribution)
    13. Lee, Y. C., Huang, H. Y., Chang, C. J., Cheng, C. H., and Chen, Y. T. (2010) Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative stress: mechanistic insight into arterial tortuosity syndrome. Human molecular genetics 19, 3721-3733
    14. Cheng, C. H., Kikuchi, T., Chen, Y. H., Sabbagha, N. G., Lee, Y. C., Pan, H. J., Chang, C., and Chen, Y. T. (2009) Mutations in the SLC2A10 gene cause arterial abnormalities in mice. Cardiovascular research 81, 381-388
    15. Saha, A., Kim, S. J., Zhang, Z., Lee, Y. C., Sarkar, C., Tsai, P. C., and Mukherjee, A. B. (2008) RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis. FEBS letters 582, 3823-3831
    16. Kim, S. J., Zhang, Z., Sarkar, C., Tsai, P. C., Lee, Y. C., Dye, L., and Mukherjee, A. B. (2008) Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice. The Journal of clinical investigation 118, 3075-3086
    17. Zhang, Z.*, Lee, Y. C.*, Kim, S. J., Choi, M. S., Tsai, P. C., Saha, A., Wei, H., Xu, Y., Xiao, Y. J., Zhang, P., Heffer, A., and Mukherjee, A. B. (2007) Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration. Human molecular genetics 16, 837-847 (*, equal contribution)
    18. Zhang, Z., Lee, Y. C., Kim, S. J., Choi, M. S., Tsai, P. C., Xu, Y., Xiao, Y. J., Zhang, P., Heffer, A., and Mukherjee, A. B. (2006) Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL. Human molecular genetics 15, 337-346
    19. Zhang, Z., Kim, S. J., Chowdhury, B., Wang, J., Lee, Y. C., Tsai, P. C., Choi, M., and Mukherjee, A. B. (2006) Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion. Gene 369, 66-71
    20. Ray, R., Zhang, Z., Lee, Y. C., Gao, J. L., and Mukherjee, A. B. (2006) Uteroglobin suppresses allergen-induced TH2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes. FEBS letters 580, 6022-6026
    21. Lee, Y. C., Zhang, Z., and Mukherjee, A. B. (2006) Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis. FEBS letters 580, 4515-4520
    22. Kim, S. J., Zhang, Z., Lee, Y. C., and Mukherjee, A. B. (2006) Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL. Human molecular genetics 15, 1580-1586
    23. Kim, S. J., Zhang, Z., Hitomi, E., Lee, Y. C., and Mukherjee, A. B. (2006) Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL. Human molecular genetics 15, 1826-1834
    24. Lee, Y. C., Lu, C. A., Casaretto, J. a., and Yu, S. M. (2003) An ABA-responsive bZIP protein, OsBZ8, mediates sugar repression of a-amylase gene expression. Physiologia Plantarum 119, 78-86
    25. Lee, Y. C., Yu, S. M., Fang, S. C., Chan, M. T., Hwa, S. F., and Liu, L. F. (1996) Sugars act as signal molecules and osmotica to regulate the expression of alpha-amylase genes and metabolic activities in germinating cereal grains. Plant Mol Biol 30, 1277-1289

     


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    115台北市南港區研究院路二段128號
    Tel: 02-27899515
    Fax: 02-27858059
    icob@gate.sinica.edu.tw
    Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:1002697--
     瀏覽人數:1002697