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曲桐(Scott C. Schuyler)

Scott C. Schuyler (曲桐)

職稱

Assistant Professor

最高學歷

Ph.D. in Cell and Developmental Biology, Harvard University, USA

E-mail

schuyler@mail.cgu.edu.tw

電話:

+886-3-211-8800 ext. 3596

傳真

+886-3-211-8700

實驗室

https://scs03596.wixsite.com/scslab

專長

Cell Biology, Cell Cycle, Protein Biochemistry, Yeast Genetics

研究方向及研究室特色

有絲分裂期間,紡錘體檢查點(Spindle checkpoint)可確保染色體正確地分裂。紡錘體檢查點在細胞中扮演著必要的角色,即使在癌細胞亦然。癌細胞展現高度的染色體分離異常及非整倍體特性,而已有假說提出紡錘體檢查點途徑的損傷為造成此表現型的原因之一。值得注意的是,受損的紡錘體檢查點途徑可能使癌細胞得以在有效的抗癌藥物之一,微管毒素(microtubule poisons)的存在下,仍可進入有絲分裂後期(anaphase)。此種有絲分裂滑移(mitotic slippage),亦即早熟型的進入有絲分裂後期,已被證實為導致癌細胞對微管毒素產生抗藥性之主要機制。有絲分裂滑移在細胞及分子上的機制至今未明。已知此現象主要牽涉兩種調控蛋白的活化,一為後期促進複合體(APC/C),另一為有絲分裂輔助因子(Cdc20)。防止「有絲分裂滑移」以促使癌細胞凋亡的相關研究日益受到重視。針對此目的,本實驗室利用出芽酵母模式系統,結合遺傳學、細胞生物學及生物化學等專業技術,進行下列兩大方向的研究:

一、開發APC/C之胜肽抑制劑

實驗室目前分析的胜肽抑制劑主要來自酵母菌的兩個蛋白: Cdc20 以及Tyc1

研究至今發現這些胜肽可與APC/C 蛋白結合並抑制 APC/C 活性。若在酵母菌活體內過度表現 Cdc20胜肽將對微管毒素 benomyl 展現較高的敏感性。未來研究目標為:

(1) 探討胜肽的最小抑制長度以及特定高保留性區域的重要性。

(2) 利用 cross-linking 生化技術以及基因篩選法找到 APC/C 上受此胜肽抑制的結合位。

(3) 發展人類的 APC/C-Cdc20 活性分析技術,並利用人類直腸癌細胞株,完成初步鑑定此新型胜肽抑制劑合併現有藥物治療的可能性。

二、篩選並研究APC/C目標受質蛋白對細胞週期進入 anaphase 的影響

 

我們已利用 Stable isotope labeling by amino acids in cell culture(SILAC) 技術篩出有絲分裂活化下 APC/C-Cdc20 的潛在受質蛋白。未來將藉由活體外 APC-Cdc20 試驗分析新發現之目標受質,並於紡錘體檢查點活化或停止時,探索有絲分裂時期 APC酵素單元體的磷酸化狀態,以研究此酵素本身的潛在調節作用。

論文與著作

Publications:

  1. Wu SY, Kuan VJ, Tzeng YW, Schuyler SC, Juang YL. (2016) The anaphase-promoting complex works together with the SCF complex for proteolysis of the S-phase cyclin Clb6 during the transition from G1 to S phase. Fungal Genet Biol. 2016 Mar 16;91:6-19.
  2. Wu CC1, Wu HJ, Wang CH, Lin CH, Hsu SC, Chen YR, Hsiao M, Schuyler SC, Lu FL, Ma N, Lu J. (2015) Akt suppresses DLK for maintaining self-renewal of mouse embryonic stem cells. Cell Cycle. 2015 Apr 15;14(8):1207-17.
  3. Gopinath RK, You ST, Chien KY, Swamy KBS, Yu JS, Schuyler SC and Leu JY. (2014) The Hsp90-dependent proteome is conserved and enriched for hub proteins with high levels of protein-protein connectivity. Genome Biology and Evolution. Oct 13;6(10):2851-65.
  4. Hsuan L, Ma C-P, Chen Y-T,Schuyler SC, Chang K-P and Tan BC. (2014)  Functional Impact of RNA Editing and ADARs on Regulation of Gene Expression: Perspectives from Deep Sequencing Studies. Cell & Bioscience. Aug 19;4:44.
  5. Liu YC, Kao YT, Huang WK, Lin KY, Wu SC, Hsu SC, Schuyler SC, Li LY, Leigh Lu F, Lu J. (2014) CCL5/RANTES is important for inducing osteogenesis of human mesenchymal stem cells and is regulated by dexamethasone. Biosci Trends. Jun;8(3):138-43.
  6. Wang CH, Ma N, Lin YT, Wu CC, Wu HJ, Yu CC, Hsiao M, Lu FL, Schuyler SC, Lu J. (2013) Array-based high-throughput screening in mouse embryonic stem cells with shRNAs. Curr Protoc Stem Cell Biol. Sep 20;26:Unit 5C.3.
  7. Huang H-N, Chen S-Y, Hwang S-M, Su M-W, Mai W, Wang H-W, Cheng W-C, Schuyler SC, Ma N, Lu FL, Lu J.  (2013) miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation.  Stem Cell Res. Dec 3;12(2):338-353.
  8. Lu FL, Yu C-C, Chiu H-H, Liu HE, Chen S-Y, Lin S, Goh T-Y, Hsu H-C, Chien C-H, Wu H-C, Chen M-S, Schuyler SC, Hsieh W-S, Wu M-H, Lu J.  (2013) Sonic hedgehog antagonists induce cell death in acute myeloid leukemia cells in the presence of lipopolysaccharides, tumor necrosis factor-α, or interferons.  Invest. New Drug.  Aug 31(4):823-32.
  9. Schuyler SC, Wu Y-F, Kuan VJ-W.  (2012) The Mad1-Mad2 balancing act - a damaged spindle checkpoint in chromosome instability and cancer.  J Cell Sci. Sep 15;125(Pt 18):4197-4206.
  10. Tzeng Y-W, Huang JN, Schuyler SC, Wu C-H, Juang Y-L.  (2011) Functions of the mitotic B-type cyclins CLB1, CLB2, and CLB3 at mitotic exit antagonized by the CDC14 phosphatase.  Fungal Genet Biol. Oct;48(10):966-78.
  11. Barnhart EL, Dorer RK, Murray AW, Schuyler SC*.  (2011) Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis.  Mol Biol Cell, Jul;22(14):2448-2457.
  12. Wu Y-P, Chang C-M, Hung C-Y, Tsai M-C, Schuyler SC, Wang RY-L*.  (2011) Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity.  Virol J. 8:128.  Erratum in: Virol J. 8:338.