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研究人員|中央研究院 細胞與個體生物學研究所

研究人員
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側邊選單開關 研究人員
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李宜靜老師實驗室

  • 李宜靜Yi-Ching Lee
    副研究員Associate Research Fellow
    • 專長:Human Genetic Diseases, Developmental Biology
    • 信箱:yiching@gate.sinica.edu.tw
    • 電話:02-2787-1550
    • 位置:R502/ICOB
實驗室簡介展開收合
GLUT10在細胞中的位置受外界環境變化影響,並影響其功能。
GLUT10 調控維生素C平衡, DNA 甲基化,基因表現,影響脂肪細胞分化,脂肪組織發育跟身體能量代謝。
建立細胞藥物篩選系統,以開發治療FGFR3 過度活化相關的軟骨發育不全和其他骨骼發育不良罕見疾病,以及相關癌症的新治療策略。

實驗室目標:

複雜疾病的發展甚至罕見疾病的發展,同時受到遺傳、環境和生活方式因素共同影響。我們研究致力於了解影響遺傳疾病風險和進展的遺傳因子和環境因子間相互作用。這些研究將提供策略以預防或延緩遺傳疾病的發展,有助於個人化醫療和開發。

我們的策略:

利用族群研究來了解遺傳疾病遺傳因子和環境間相互作用,但仍然極具挑戰性。我們實驗室目前從了解罕見疾病的致病基因和致病途徑開始,近一步了解影響發病途徑的環境因子,來研究相關的複雜遺傳疾病。

目前研究主題:

我們目前研究專注於結締組織疾病,因為許多老化常見疾病與結締組織有關,而且遺傳因子和以及飲食和生活習慣對這些疾病的發展有很大影響。包含心血管,骨骼,關節,代謝,癌症相關疾病。

1.了解罕見的結締組織疾病,致病基因功能和致病途徑。動脈迂曲綜合徵(ATS)是由於葡萄糖轉運蛋白10 (GLUT10) 基因突變,引起功能缺失所造成。ATS許多病徵與老化相關的結締組織疾病相似。我們利用小鼠與細胞系統,研究GLUT10功能、影響結締組織發育及功能維持。
2.了解致病基因功能和致病途徑,如何與年齡、飲食和微環境變化交互作用,影響相關疾病進展。利用小鼠與細胞系統,了解環境變化如何影響GLUT10功能與其發病途徑,影響ATS進展。進而在ATS患者,跟發病途徑相關常見結締組織疾病族群做更近一步驗證。
3.開發治療FGFR3 過度活化相關的軟骨發育不全 (ACH)和其他骨骼發育不良罕見疾病,以及相關癌症的新治療策略。我們建立藥物篩選系統,ACH和癌症小鼠模式,更進一步暸解致病機制,並開發治療策略。

我們也積極參與合作研究,暸解跟疾病相關基因,發病機制,並開發潛在的診斷和預防策略。希望這些研究將提供策略以預防或延緩遺傳疾病的發展,有助於個人化醫療和開發。

實驗室成員展開收合
姓名 職稱 電話 Email 備註
李宜靜 副研究員 02-27871550 yiching@gate.sinica.edu.tw
林韻文 博士班研究生 02-27871549
周安努 博士班研究生 02-27871549
Abhishek Negi 博士班研究生 02-27871549
阮秋莊 研究助理 02-27871549
著作展開收合

1.     Jiang Chung-Lin, Tsao Chang-Yu, Lee Yi-Ching*, 2022, “Vitamin C attenuates predisposition to high-fat diet-induced metabolic dysregulation in GLUT10-deficient mouse model”, Genes & Nutrition, 17(1), doi: 10.1186/s12263-022-00713-y. 

2.     Johnson TA, Mashimo Y, Wu JY, Yoon D, Hata A, Kubo M, Takahashi A, Tsunoda T, Ozaki K, Tanaka T, Ito K, Suzuki H, Hamada H, Kobayashi T, Hara T, Chen CH, Lee YC, Liu YM, Chang LC, Chang CP, Hong YM, Jang GY, Yun SW, Yu JJ, Lee KY, Kim JJ, Park T, Lee JK, Chen YT, Onouchi Y, 2021, “Association of an IGHV3-66 gene variant with Kawasaki disease.”, Journal of human genetics, 66(5), 475-489. 

3.     Wagner BM, Robinson JW, Lin YW, Lee YC, Kaci N, Legeai-Mallet L, Potter LR, 2021, “Prevention of guanylyl cyclase-B dephosphorylation rescues achondroplastic dwarfism.”, JCI insight, 6(9):, e147832. 

4.     Tseng TL, Wang YT, Tsao CY, Ke YT, Lee YC, Hsu HJ, Poss KD, Chen CH, 2021, “The RNA helicase Ddx52 functions as a growth switch in juvenile zebrafish.”, DEVELOPMENT, 2, 2-23. 

5.     Jiang, C.L., Jen, W.P., Tsao, C.Y., Chang, L.C., Chen, C.H., Lee, Y.C.*, 2020, “Glucose Transporter 10 Modulates Adipogenesis via Ascorbic Acid-Mediated Pathway to Protect Mice Against Diet-Induced Metabolic Dysregulation.”, PLOS Genetics, 16 (5): e1008823. 

6.     Jen WP, Chen HM, Lin YS, Chern Y, Lee YC*, 2020, “Twist1 Plays an Anti-apoptotic Role in Mutant Huntingtin Expression Striatal Progenitor Cells.”, Molecular neurobiology, 57(3), 1688-1703. 

7.     Ko TM, Chang JS, Chen SP, Liu YM, Chang CJ, Tsai FJ, Lee YC, Chen CH, Chen YT, Wu JY, 2019, “Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.”, Scientific reports, 9,328. 

8.     Syu YW, Lai HW, Jiang CL, Tsai HY, Lin CC, Lee YC*, 2018, “GLUT10 maintains the integrity of major arteries through regulation of redox homeostasis and mitochondrial function.”, Human molecular genetics, 27(2), 307-321. 

9.     Lenka G, Tsai MH, Lin HC, Hsiao JH, Lee YC, Lu TP, Lee JM, Hsu CP, Lai LC, Chuang EY, 2017, “Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma.”, Scientific reports, 7, 42573. 

10.  Lee YC*, Song IW, Pai YJ, Chen SD, Chen YT, 2017, “Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia.”, Scientific reports, 7, 43220. (*: corresponding author)

11.  Ko TM, Kuo HC, Chang JS, Chen SP, Liu YM, Chen HW, Tsai FJ, Lee YC, Chen CH, Wu JY, Chen YT, 2015, “CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease.”, Circulation research, 116(5), 876-83. 

12.  Lin YC, Lee YC, Li LH, Cheng CJ, Yang RB, 2014, “Tumor suppressor SCUBE2 inhibits breast-cancer cell migration and invasion through the reversal of epithelial-mesenchymal transition.”, Journal of cell science, 127(Pt 1), 85-100. 

13.  Chen CH, Lee CS, Lee MT, Ouyang WC, Chen CC, Chong MY, Wu JY, Tan HK, Lee YC, Chuo LJ, Chiu NY, Tsang HY, Chang TJ, Lung FW, Chiu CH, Chang CH, Chen YS, Hou YM, Chen CC, Lai TJ, Tung CL, Chen CY, Lane HY, Su TP, Feng J, Lin JJ, Chang CJ, Teng PR, Liu CY, Chen CK, Liu IC, Chen JJ, Lu T, Fan CC, Wu CK, Li CF, Wang KH, Wu LS, Peng HL, Chang CP, Lu LS, Chen YT, Cheng AT, 2014, “Variant GADL1 and response to lithium therapy in bipolar I disorder.”, The New England journal of medicine, 370(2), 119-28. 

14.  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.C., Hong, Y. M., Jang, G. Y., Hibberd, M. L., Kuijpers, T., Burgner, D., Levin, M., Burns, Davila, J. S, International Kawasaki Disease Genetics Consortium, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium, Chen, Y.T., Chen, C. H., Wu, J. Y. & 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(8), e72037. 

15.  Lee YC, Kuo HC, Chang JS, Chang LY, Huang LM, Chen MR, Liang CD, Chi H, Huang FY, Lee ML, Huang YC, Hwang B, Chiu NC, Hwang KP, Lee PC, Chang LC, Liu YM, Chen YJ, Chen CH, Chen YT, Tsai FJ, Wu JY, 2012, “Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis.”, Nature genetics, 44(5), 522-525. 

16.  Khor, C. C., ¶ Davila, S., ¶ Breunis, W. B., ¶ Lee, Y. C., ¶ Shimizu, C., Wright, V. J., Yeung, R., Tan, D. E. K., Wang, J. J., Wong, T. Y., 2011, “Genome-wide association study in five independent cohorts identifies FCGR2A as a susceptibility factor for Kawasaki disease.”, Nature Genetics, 43(12), 1241-1246. (¶: equal contribution)

17.  Lee, Y.C., Chang, C.J., Chen, Y.T., and Yan, Y.T. *, 2011, “Glycogen-Branching Enzyme Deficiency Leads to Abnormal Cardiac Development: Novel Insight into Glycogen Storage Disease IV. ”, Human molecular genetics, 20, 455-465. 

18.  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., Liu,Y.M., Wang, H.W., 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(2), e16853. (¶: equal contribution)

19.  Cheng P.Y., Lin Y.P., Chen Y.L., Lee Y.C.,Tai C.C., et al. , 2011, “Interplay between SIN3A and STAT3 Mediates Chromatin Conformational Changes and GFAP Expression during Cellular Differentiation. ”, PLoS ONE, 6(7), e22018. 

20.  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(14), 10822-10831. (¶: equal contribution)

21.  Lee, Y.C., Huang, H.Y., Chang, C.J., Cheng, C.H., and Chen, Y.T. , 2010, “Mitochondrial Glucose Transporter 10 Facilitates Dehydroascorbic Acid Import and Protects Cells Against Oxidative Stress: Mechanistic Insights into Arterial Tortuosity Syndrome. ”, Human molecular genetics, 19(19), 3721-3733. 

22.  Cheng CH, Kikuchi T, Chen YH, Sabbagha NG, Lee YC, Pan HJ, Chang C, Chen YT, 2009, “Mutations in the SLC2A10 gene cause arterial abnormalities in mice.”, Cardiovascular research, 81(2), 381-388. 

23.  Kim SJ, Zhang Z, Sarkar C, Tsai PC, Lee YC, Dye L, Mukherjee AB, 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(9), 3075-3086. 

24.  Saha A, Kim SJ, Zhang Z, Lee YC, Sarkar C, Tsai PC, Mukherjee AB, 2008, “RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis.”, FEBS letters, 582(27), 3823-3831. 

25.  Zhang Z¶, Lee YC¶, Kim SJ, Choi MS, Tsai PC, Saha A, Wei H, Xu Y, Xiao YJ, Zhang P, Heffer A, Mukherjee AB, 2007, “Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration.”, Human molecular genetics, 16(7), 837-847. (¶: equal contribution)

26.  Kim SJ, Zhang Z, Hitomi E, Lee YC, Mukherjee AB, 2006, “Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL.”, Human molecular genetics, 15(11), 1826-1834. 

27.  Zhang Z, Kim SJ, Chowdhury B, Wang J, Lee YC, Tsai PC, Choi M, Mukherjee AB, 2006, “Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion.”, Gene, 369, 66-71. 

28.  Lee YC, Zhang Z, Mukherjee AB, 2006, “Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis.”, FEBS letters, 580(18), 4515-4520. 

29.  Kim SJ, Zhang Z, Lee YC, Mukherjee AB, 2006, “Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL.”, Human molecular genetics, 15(10), 1580-1586. 

30.  Zhang Z¶, Lee YC¶, Kim SJ, Choi MS, Tsai PC, Xu Y, Xiao YJ, Zhang P, Heffer A, Mukherjee AB, 2006, “Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.”, Human molecular genetics, 15(2), 337-346. (¶: equal contribution)

31.  Ray R, Zhang Z, Lee YC, Gao JL, Mukherjee AB, 2006, “Uteroglobin suppresses allergen-induced TH2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes.”, FEBS letters, 580(25), 6022-6026. 

32.  Lee, Y.C., Lu, C.A., Casaretto, J.a., and Yu, S.M., 2003, “An ABA-responsive bZIP protein, OsBZ8, mediates sugar repression of ?-amylase gene expression.”, Physiologia Plantarum, 119(1), 78-86. 

33.  Yu SM¶, Lee YC¶, Fang SC, Chan MT, Hwa SF, Liu LF, 1996, “Sugars act as signal molecules and osmotica to regulate the expression of alpha-amylase genes and metabolic activities in germinating cereal grains.”, Plant molecular biology, 30(6), 1277-1289. (¶: equal contribution)