徐欣伶研究員

徐欣伶  研究員
分子與基因醫學研究所
電話:886-37-206166 ext. 35329
E-mail:hsinling88@nhri.edu.tw

 

 

 

 

 

學歷

-Ph.D., Department of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan (1996)
-B.S., Department of Biology, Tung-Hai University, Taichung, Taiwan (1987)

經歷

2022/07 – present

Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, R.O.C.

2011/10 – 2022/06

Associate Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, R.O.C.

2004 – 2011/09

Assistant Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, R.O.C.

2002 – 2004

Research Assistant Professor, -, Northwestern University Medical School, Chicago, IL

2001 – 2002

Scientist/Biochemist, -, Lawrence Berkeley National Laboratory, Berkeley, CA

1999 – 2001

Postdoctoral Fellow in Biochemistry, -, Lawrence Berkeley National Laboratory, Berkeley, CA

1996 – 1999

Postdoctoral Fellow in Biochemistry, -, Los Alamos National Laboratory, Los Alamos, NM

1987 – 1989

Instructor, -, Tung-Hai University, Taichung, Taiwan

研究興趣

        本研究團隊進行基礎與應用性研究,主題包括為: 遺傳物質修補功能、染色體結構完整性、及致癌基因誘發細胞病變機轉。運用細胞株及動物個體研究模式,針對乳癌及肺癌形成機轉進行研究。 
        我們早期研究發現自體免疫蛋白Ku及DNA激脢蛋白(DNA-PKcs)共同參與雙股DNA斷裂修補工作。進一步探討發現Ku及DNA-PKcs在穩定基因體末端架構上伴演重要角色。Ku及DNA-PKcs基因缺失之轉殖鼠細胞呈現染色體末端異常結合形態、縮短染色體長度、加速細胞老化過程、且該動物體易罹患腫瘤病變。實驗證明Ku與染色體末端結合蛋白TRF1具功能性密切交互作用,藉此TRF1/Ku蛋白質體間直接結合,藉以調節染色體末端結構穩定。目前我們正積極從事基因體修補能力及染色體結構整合層面,探索正常細胞的基因體監控調節如何被擾亂導致轉型為癌細胞。
        一方面我們的研究主題針對致癌基因作用機制。新致癌基因MCT-1蛋白質過量表達導致細胞快速增殖、擾亂基因體監視激脢訊息傳導途徑、及持續過度活化DNA修補蛋白脢活性。我們已明顯觀測到MCT-1蛋白嚴重造成多條染色質錯誤連結、遺傳物質轉移、及異常複製現象。增加MCT-1在肺細胞或乳腺細胞表現量,我們可檢測細胞轉化能力、抗癌試劑抗藥性、及基因體結構破壞程度,來剖析基因變異及細胞生理功能惡化機轉。針對抑制MCT-1在癌細胞表現活性,是否可減緩癌細胞增殖能力、提升癌細胞對藥物化學及放射物理療法感受度,預期評估MCT-1基因調控在醫療運用價質。MCT-1基因轉殖鼠技術配合生物化學研究及組織切片分析,將輔助證明體外細胞實驗數據結果。綜合上述之研究成果將益助於早期診斷、治療及預防癌細胞轉移惡化之可能性。
        隨著「後基因體時期」(post-genomic era) 時代來臨,對於基因之結構與功能的瞭解非常迅速,使得我們能據以觀察分析,找出在疾病演生時呈現異常表現的基因。這些基因資訊不僅能顯示疾病的分子遺傳機轉,也發展診斷及治療方法的重要標的。

榮譽與獲獎

2008-2011 NRPGM Grant Award, NSC

2007-2010 Young Investigator Career Development Award, NSC

2001 Telomere Award Given by the Telomere and Telomerase Meeting, Cold Spring Harbor

1996 1ST Prize of Dr. Chien-Tien Hsu’s Science Award Given by the Chinese Society of Cell and Molecular Biology, Taiwan

1989-1996 Pre-doctoral Fellowship, National Yang-Ming University, Taipei, Taiwan

學術著作

  1. Hsu HL, Gilley D, Blackburn EH, Chen DJ. (1999) Ku is associated with the telomere in mammals. Proc. Natl. Acad. Sci. U S A 96:12454-12458. (IF. 10.26) 
  2. Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ. (2000) Ku acts in a unique way at the mammalian telomere to prevent end joining. Gene. Dev. 14:2807-2812. (IF. 19.676)
  3. Hsu HL, Shi B, Gartenhaus RB. (2005) The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene. 24:4956-4964. (IF. 6.872)
  4. Shih HJ, Chu KL, Wu MH, Wu PH, Chang WW, Chu JS, Wang LH, Takeuchi H, Ouchi T, Hsu HL*. (2012) The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities. Cell Cycle. 11: 934-952. (*corresponding author) (IF. 5.243), 44/185/Cell Biology (23.7%)
  5. Shih HJ, Chen HH, Chen YA, Wu MH, Liou GG, Chang WW, Chen L, Wang LH, Hsu HL*. (2012) Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity. Oncotarget. 2012. 3:1401-15. (*corresponding author) (IF 6.636), 21/197/Oncology (10.65%)
  6. Wu MH, Chen YA, Chen HH, Chang KW, Chang IS, Wang LH, Hsu HL*. MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation. Oncogene, 33:5109 (2014) (*corresponding author). (IF 8.459), 13/211/Oncology (6.16%)
  7. Tseng HY, Chen YA, Jen J, Shen PC, Chen LM, Lin TD, Wang YC and Hsu HL*. Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression. Oncogenesis 6, e313 (2017). (*corresponding author). (IF 4.722), 54/223/Oncology (24.2%)
  8. Chen LM, Liu PY, Chen YA, Tseng HY, Shen PC,Hwang PA and Hsu HL*. Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression. Scientific Reports. (2017, 7:11864). (*corresponding author) (IF. 4.122), 12/64/MULTIDISCIPLINARY SCIENCES (18.75%)
  9. Weng YS, Tseng HY, Chen YA, Shen PC,Al Haq AT, Chen LM, Tung YC and Hsu HL*. MCT-1/IL-6/IL-6R signaling modulates EMT progression, cancer stemness and microenvironment in aggressive breast cancer. (Molecular Cancer, in press, 2019) (*corresponding author) (IF. 10.679) 11/229/Oncology (4.8%)
  10. Chen LM, Tseng HY, Chen YA, Al Haq AT, Hwang PA, Hsu HL*. Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression. Cancers (2020, 12(2). pii: E421 ) (*corresponding author) (IF. 6.12) 31/230 Oncology(13.4%)

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