Dr. Lee, Eminy H.Y. 's publons link picture

李小媛博士

特聘研究員
  • 02-27899125 (Lab) (Room No: 308)
  • 02-27829224 (Fax)

Specialty:
  • Pathogenesis of and Neuroprotection against Alzheimer's Disease
  • Molecular Mechanism of Mammalian Long-Term Memory Formation

Education and Positions:
  • Ph.D. Univ. of California, San Diego


我們實驗室的研究興趣之一是探討阿茲海默症的病理成因及其神經保護機制。近期我們發現galectin-3這個醣蛋白會促進神經發炎並且是造成阿茲海默症的重要成因。Galectin-3在海馬迴的表現量在年輕的APP/PS1小鼠就有明顯的增加,因此,galectin-3可能可以做為阿茲海默症的一種生物指標及新穎的治療標的。在探討阿茲海默症的神經保護機制方面,我們發現蛋白質的類小泛素化扮演一個重要的角色。例如:Elk-1的類小泛素化會降低GADD45a 的表現並減少APP/PS1小鼠海馬迴的神經細胞凋亡。AICD的類小泛素化會增加AICD進核的能力,進而增加 neprilysin 及 transthyretin 的表現並促進APP/PS1小鼠腦中類澱粉蛋白的降解。我們目前正在探討APP蛋白類小泛素化的神經保護角色及機制,我們也要確認可以引發APP類小泛素化的內生性刺激以及探索其他的內生性神經保護機制。這些研究結果將使我們對於阿茲海默症的病理成因有嶄新的瞭解及新穎的治療策略。

 

本實驗室的另一項研究興趣是探討哺乳動物長期記憶形成的神經和分子生物機制。在確認了一個參與記憶形成的候選基因之後,我們會進一步探討其表現量,訊息傳遞途徑以及對記憶的調控機制。先前,利用PCR差異表現法,我們曾經確認了sgk 基因和 pias1 基因在長期記憶形成中的新穎角色和機制。Sgk 基因的確認使科學家對於醣皮質素在人類和動物能促進記憶提供了一個很好的分子生物學上的詮釋。Pias1 基因的確認則揭露了蛋白質的類小泛素化在長期記憶形成中所扮演的重要角色。利用同樣的 PCR 差異表現法策略,我們最近還確認了其他的新穎候選基因,目前我們正在探討這些基因在長期記憶中的角色及其對記憶形成的調控機制。

Our Team
Team photo

期刊 94 專書 0

  1. Liu Y.C., Hsu W.L., Ma Y.L. and Lee E.H.Y.* Melatonin induction of APP intracellular domain 50 SUMOylation alleviates Alzheimer\'s disease through enhanced transcriptional activation and Abeta degradation Molecular Therapy 29, 376-395 (2021-01) [JCR] [WOS]
  2. Hsu W.L., Ma Y.L., Liu Y.C., Tai D.J.C. and Lee E.H.Y.* Restoring Wnt6 signaling ameliorates behavioral deficits in MeCP2 T158A mouse model of Rett syndrome Scientific Reports 10, 1074 (2020-02) [JCR] [WOS]
  3. Tao C.C., Cheng K.M., Ma Y.L., Hsu W.L., Chen Y.C., Fuh J.L., Lee W.J., Chao C.C. and Lee E.H.Y.* Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer’s disease Cell Death and Differentiation 27(1),192-209 (2020-01) [JCR] [WOS]
  4. Liu S.Y., Ma Y.L., Hsu W.L., Chiou H.Y. and Lee E.H.Y.* Protein inhibitor of activated STAT1 Ser503 phosphorylation‐ mediated Elk‐1 SUMOylation promotes neuronal survival in APP/PS1 mice British Journal of Pharmacology 176(11),1793-1810 (2019-06) [JCR] [WOS]
  5. Hsu W.L., Ma Y.L., Liu Y.C. and Lee E.H.Y.* Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2 BMC Biology 15(1), 112. (2017-11) [JCR] [WOS]
  6. Chen Y.C., Ma Y.L., Lin C.H., Cheng S.J., Hsu W.L. and Lee E.H.Y.* Galectin-3 negatively regulates hippocampus-dependent memory formation through inhibition of integrin signaling and galectin-3 phosphorylation Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2017.00217,10, 1-15 (2017-07) [JCR] [WOS]
  7. Tao C.C., Hsu W.L., Ma Y.L., Cheng S.J. and Lee E.H.Y.* Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Abeta toxicity in a mouse model of Alzheimer’s disease Cell Death and Differentiation 24, 597-614 (2017-04) [JCR] [WOS]
  8. Tai J.C.§, Liu Y.C.§, Hsu W.L.§, Ma Y.L., Cheng S.J., Liu S.Y. and Lee E.H.Y.* MeCP2 SUMOylation rescues Mecp2 mutant-induced behavioral deficits in a mouse model of Rett syndrome Nature Communications 7, 10552 (2016-02) [JCR] [WOS]
  9. Lin C.H., Liu S.Y. and Lee E.H.Y.* SUMO-modification of Akt enhances global SUMOylation and substrate SUMOylation specificity through Akt phosphorylation of Ubc9 and SUMO1 Oncogene 35, 595-607 (2016-02) [JCR] [WOS]
  10. Chen Y.C.§, Hsu W.L.§, Ma Y.L., Tai J.C. and Lee E.H.Y.* CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory J. Neuroscience 34, 9574-9589 (2014-07) [JCR] [WOS]