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柯博元

 

柯博元

職稱助理教授

研究室名稱細胞壓力反應之分子機制研究室

最高學歷博士

學校/國家國立台灣大學醫學院/台灣

分機號碼5115

電子郵件帳號 pyke0324@mail.cgu.edu.tw

個人網頁網址:

研究室現有: 博士後研究員  

博士班研究生  1

碩士班研究生 2

專任研究助理  1

大學部專題生    

Update2016/07/07

研究方向研究室特色

細胞自噬作用(Autophagy)是一種經由細胞遭遇壓力(如營養缺乏)所引發的一種細胞反應,自噬作用藉由細胞內膜構造的重組以及一連串訊息傳遞而產生前自噬體(preautophagosome),再形成雙層膜構造(Isolation membrane/phagophore),藉由此雙層膜結構包覆細胞質成為自噬體(autophagosome),隨之自噬體便與溶小體結合為溶自噬體(autolysosome),將其包覆之內含物分解。細胞自噬作用對於清除細胞內蛋白質的堆疊、破損的胞器以及外來感染的病原體扮演非常重要的角色,研究細胞自噬作用對於了解細胞如何抗細胞所面臨壓力至為重要。本研究室未來有下列幾個方向:

 

(1)       許多病毒的感染被發現會引起細胞自噬作用以促進病毒的複製,以C型肝炎為例,我們過去的研究(Journal of Clinical Investigation, 2011), 發現病毒感染宿主細胞會經由不正常蛋白質堆疊反應(unfolded protein response)引發自噬作用,而自噬作用則透過抑制即時性抗病毒免疫力的活化來促進病毒RNA基因體的複製。因循這些結果,未來本研究室利用分子生物學、蛋白質體學方法以及電子顯微鏡技術繼續探討細胞自噬作用如何透過調節調控即時性免疫反應訊息傳遞或是分子的運輸以抑制抗病毒免疫反應的活化。

 

(2)       許多病毒所引發之自噬作用多半透過不正常蛋白質堆疊反應而活化,截至目前為止,其詳細的分子機制依然不清楚;目前的研究顯示,由於病毒大多於內質網(endoplasmic reticulum)所形成的膜狀構造進行複製而產生的內質網壓力(endoplasmic reticulum stress),因而誘發不正常蛋白質堆疊反應,再進而活化細胞自噬作用,本研究室將來將利用干擾性RNA以及轉錄基因體學的方法來探討究竟是什麼樣的分子在不正常蛋白質堆疊所引發的細胞自噬作用扮演重要的角色,而其透過的是什麼樣的分子機制,包括,基因轉錄、蛋白質新合成或是蛋白質轉錄後修飾等。

 

(3)       細胞自噬作用對於癌細胞發生及演進既是促進者也是抑制者的角色,目前對於噬作用在癌症形成的過程其確切角色的相關研究結論依舊是混沌不清的,因此本研究室將對細胞自噬作用在國人常見的肝癌發生過程中扮演的功能角色進行探討。

 

 

最近五年所發表論文:

Journal articles:

1. Autophagy in hepatitis C virus-host interactions: Potential roles and therapeutic targets for liver-associated diseases.

Ke, P.Y. and Chen, S,S-L.

World Journal of Gastroenterology 20: 5773-5793, 2014

2. RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication.

Wu MJ, Ke P.Y., Horng J.T.

Biochem Biophys Res Commun. 454: 19-24, 2014

3. Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction.

Wu, M.J., Ke, P.Y., Hsu, J.T., Yeh, C.T., and Horng, J.T.

Cellular Microbiology 16: 1603-1618, 2014.

4. Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism.

Tseng, Y.H., Ke, P.Y., Liao, C.J., Wu, S.M., Chi, H.C., Tsai, C.Y., Chen, C.Y., Lin, Y. H., and Lin, K.H.

   Autophagy 10: 20-31, 2014.

5. Active RNA replication of hepatitis C virus downregulates CD81 expression.

Ke, P.Y. and Chen, S.S-L.

   PLoS ONE 8: e54866, 2013.

6. An occult hepatitis B-derived hepatoma cell line carrying persistent nuclear viral DNA and permissive for exogenous hepatitis B virus infection.

Lin, C.L., Chien, R.N., Lin, S.M., Ke, P.Y., Lin, C.C., and Yeh, C.T.

PLoS ONE 8: e65456, 2013.

7. Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases.

Ke, P.Y. and Chen, S.S.L.

Viruses 4: 2251-2290, 2012.

8. Guidelines for the use and interpretation of assays for monitoring autophagy.

Daniel J. Klionsky et al., and Ke, P.Y., and 1269 authors.

Autophagy 8; 4:1-100, 2012.

9. Autophagy: a new guardian of HCV against innate immune response.

   Ke, P.Y. and Chen, S.S-L.

   Autophagy 7: 533-535, 2011.

10. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro.

Ke, P.Y. and Chen, S.S-L.

Journal of Clinical Investigation 121: 37-56, 2011.

u SciBX editorial board recommended

u Journal of Hepatology editorial board recommended

11. Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane go41 protein as a distinct determinant for viral infection.  

    Chen, S.S-L., Yang, P., Ke, P.Y., Li, H.F., Chan, W.E., Chang, DK., Chuang C.K., Tsai, Y., and Huang, S.C.  

    Journal of Virology 83: 870-883, 2009.

12. Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding.

    Ke, P.Y., Hu, C.M., Chang, Y.C., and Chang, Z.F.

    FASEB Journal 21: 1276-1284, 2007.

13. Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability.

    Ke, P.Y., Kuo, Y.Y., Hu, C.M., and Chang, Z.F.

    Genes & Development 19: 1920-1933, 2005.

u Faculty of 1000 in Biology recommended with a score of 10.

14. Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site.

    Li, C.L., Lu, C.Y., Ke, P.Y., and Chang, Z.F.

 

Books:

1. Suppression of innate antiviral immunity after hepatitis C virus infection: role of the unfolded protein response and autophagy.

Chen, S.S-L. and Ke, P.Y. 

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging: Volume 2 - Role in General Diseases Chapter 9. (ISBN: 9780124058774). Amsterdam, Netherlands: ELSEVIER. Dec, 2013.

2. Multifaceted Roles of Autophagy in the Life Cycle of Flaviviridae.

Ke, P.Y. and Chen, S.S-L.

Recent Research Developments in Virology, Vol. 8. (ISBN: 978-81-7895-563-6). Kerala, India: Transworld Research Network. Apr, 2012.

 

Awards & Honors:

l  2003  Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine

l  2003  International Conference Travel Award, The Chinese Society of Cell and Molecular Biology

l  2004  Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology

l  2004  Outstanding Student Award in Academy, National Taiwan University

l  2005  Post-doctoral Fellowship Award, National Health Research Institute

l  2005  The President Award in Medicine and Technology, Tien-Te Lee Biomedical Foundation, Yung Shin PHARM. IND. CO., LTD

l  2009  Poster Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology

l  2010  Poster Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology

l  2010  Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica

l  2010  International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses

l  2011  Outstanding Paper Award on hepatitis C virus research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C.

l  2014  科技部補助大專校院獎勵特殊優秀人才

l  2015  科技部補助大專校院獎勵特殊優秀人才

 

Board Certification:

Peer Reviewer:  Autophagy; Viruses; Apoptosis

 

Ongoing projects:

1. Functional study of autophagic response in suppression of type I interferon response (NSC102-2320-B-182-037-MY3, 102/8/1~105/7/30)

2. Deciphering HCV-host interactions by identifying substrates of viral-induced selective autophagy (NHRI-EX103-10322SC, 103/1/1~106/12/30)

3. Study on the Functional Role of Selective Autophagy in Hepatitis C Virus Life Cycle (CMRPD1D0021, 103/1/1~105/12/30)

 

         

 

 

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