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柯博元

職稱：副教授

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

研究室現有：博士班研究生  1 人， 碩士班研究生 1人，專任研究助理  1 人，大學部專題生  5 人，Update：2022/08/04 

研究方向及研究室特色：

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拮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，目前對於自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。

 

 

Current position:

Assistant Professor

Department of Biochemistry & Molecular Biology and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taiwan, Republic of China

Liver Research Center, Chang Gung Memorial Hospital, LinKuo, Taiwan, Republic of China

Contact information:

Tumor Research Laboratory

The 6th Floor, 1st Medicine Building

No. 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan,Taiwan33302, R.O.C

Tel: +886-3-2118800 ext 5115

Education:

Ph.D.    Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taiwan, Republic of China

Relevant experience:

Postdoctoral Research Fellow in Institute of Biomedical Sciences, Academia Sinica (2007/3~ 2012/2)

Postdoctoral Research Fellow in Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University (2005/7~2005/11)

Fields of specialty:

Protein degradation, Autophagy, Selective autophagy, Hepatitis C virus, and Liver-associated diseases, Molecular virology

                                                       

HONORS & ACADEMIC SERVICE

(I) AWARDS

  1. 全球前 2% 頂尖科學家(World’s Top 2% Scientists) 獲獎人(2021).
  2. 長庚大學108年度優良教師獎(2019)
  3. 科技部傑出學者養成計畫 (MOST grant award for cultivation of outstanding young scholars，支持105~108三年期研究計畫)獲獎人
  4. 國家衛生研究院 (NHRI)103年度Career Development Grant (CDG，支持103-107四年期研究計畫)獲獎人
  5. 科技部補助大專校院獎勵特殊優秀人才(2015)
  6. 科技部補助大專校院獎勵特殊優秀人才(2014)
  7. Outstanding Paper Award on Hepatitis C Virus Research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C. (2011)
  8. International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses (2011)
  9. Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica (2010)
  10. Poster Outstanding Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology (2010)
  11. Poster Outstanding Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology (2009)
  12. The President Award in Medicine and Technology, Tien-Te Lee Biomedical
  13. Foundation, Yung Shin PHARM. IND. CO., LTD (2005)
  14. Post-doctoral Fellowship Award, National Health Research Institute (2005)
  15. Outstanding Student Award in Academy, National Taiwan University (2004)
  16. Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology (2004)
  17. International Conference Travel Award, The Chinese Society of Cell and Molecular Biology (2003)
  18. Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine (2003)

(II) ACADEMIC SERVICE

  1. The editorial board member of Scientific Reports (SCI) (2019~)
  2. The editorial board member of Pathogens (SCI) (2019~)
  3. The editorial board member of Frontier in Microbiology (SCI) (2021~)
  4. The reviewer board member of International Journal of Molecular Sciences (SCI) (2020~)
  5. The reviewer board member of Cells (SCI) (2020~)
  6. The reviewer board member of Microorganisms (SCI) (2020~)
  7. The review board member of Welcome Trust Investigator Grant Award 2020 (UK) (2020)
  8. The 9th International Symposium on Autophagy (2019) Organization Committee and Section Chair
  9. The peer reviewer of research journals (SCI): Autophagy; Viruses; Apoptosis; Scientific Reports; Journal of Biomedical Sciences; Brain Research; Cell cycle; Biomedical Journal; Cellular Microbiology; IJMS; Cells; Cancers; Journal of Virology; PLoS ONE; BioMed Research International
  10. The peer reviewer of research proposal and funding grant: Ministry of science and technology (MOST) research proposal; Chang Gung Memorial Hospital (CGMH) research proposal; Taipei Veterans General Hospital (TVGH) research proposal; Cheng Hsin General Hospital (CHGH) research proposal

(III) MEMBERSHIP

  1. The Chinese Society of Cell and Molecular Biology (2001-present)
  2. The American Society of Cell Biology (2004-present)
  3. The International Conference of Hepatitis C Virus and Related Virus (2010-present)
  4. The Gordon Research Conference: Autophagy (2014-present)
  5. The International Symposium of Autophagy, Asia (2014-present)
  6. Keystone Symposium in Molecular and Cellular Biology (2015-present)
  7. Cold Spring Harbor Conferences, Asia (2015-present) 

GRNAT SUPPORT

  1. 探索專一性粒腺體自噬作用在黃熱病毒與宿主交互作用之生理角色(MOST 109-2320-B-182-010-MY3) (2020/8/1~2023/7/31) (NT$ 5,760,000), 補助機構: 科技部
  2. 探討人類DEAD-box helicase 3所導引之細胞自噬脂質分解作用於黃熱病毒感染與宿主細胞交互作用之生理功能性角色(MOST 108-2320-B-182-011) (2019/8/1~2020/7/31) (NT$ 1,309,000), 補助機構: 科技部
  3. 專一細胞自噬反應引發之選擇性分解作用於調控病毒接受體分子與病毒感染力交互作用之功能性分析(MOST 105-2628-B-182-001-MY3) (2016/8/1~2019/7/31) (NT$ 4,295,000), 補助機構: 科技部
  4. 探索C型肝炎病毒引發之專一選擇性細胞自噬作用降解的分子以研究病毒與宿主細胞之交互作用, (NHRI-EX103 ~106-10322SC) (2014/1/1~2017/12/31) (NT$ 7,000,000), 補助機構: 國家衛生研究院
  5. 細胞自噬分解作用於負向調控第一型干擾素反應之功能性分析, (MOST 102-2320-B-182-037-MY3) (2013/8/1~2016/7/31) (NT$ 6,528,000), 補助機構: 科技部
  6. 探討selective autophagy調控RLR抗病毒訊息傳遞之分子機轉, (MOST 101-2320-B-182-043) (2012/8/1~2013/7/31) (NT$ 1,050,000), 補助機構: 科技部

Publications:

Journal articles:

  1. Liou LB, Wang TY, Liu IJ, Wu HC, Ke PY, Fang YF, Chen YF, α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study, LUPUS, Jul, 2022, 31(8): 927-938.
  2. Ke PY, Chang CW, Hsiao YC, Baicalein Activates Parkin-Dependent Mitophagy through NDP52 and OPTN, Cells, Mar, 2022, 11(7): 1132.
  3. Ke PY, Autophagy and antiviral defense, IUBMB Life, Apr, 2022, 74(4): 317-338.
  4. Peng HH, Wu CY, Hsiao YC, Martel J, Ke PY, Chiu CY, Liau JC, Chang IT, Su YH, Ko YF, Young JD, Ojcius DM, Ganoderma lucidum stimulates autophagy-dependent longevity pathways in Caenorhabditis elegans and human cells, Aging-us, May, 2021, 13(10): 13474-13495.
  5. Klionsky DJ et al, and Ke PY, and 2290 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy, Jan, 2021, 17(1): 1-382.
  6. Lin CL, Chien RN, Chu YD, Liang KH, Huang YH, Ke PY, Lin KH, Lin YH, Yeh CT, Hepatitis B virus X gene mutants emerge during antiviral therapy and increase cccDNA levels to compensate for replication suppression, Hepatology International, Dec, 2020, 14(6): 973-984.
  7. Ke PY, Mitophagy in the Pathogenesis of Liver Diseases, Cells, Mar, 2020, 9(4): 831.
  8. Martel J, Ojcius DM, Ko YF, Ke PY, Wu CY, Peng HH, Young JD, Hormetic Effects of Phytochemicals on Health and Longevity, Trends in Endocrinology & Metabolism, Jun, 2019, 30(6): 335-346.
  9. Lai MW, Chu YD, Lin CL, Chien RN, Yeh TS, Pan TL, Ke PY, Lin KH, Yeh CT, Is there a sex difference in postoperative prognosis of hepatocellular carcinoma?, BMC Cancer, Mar, 2019, 19(1): 250.
  10. Ke PY, Diverse Functions of Autophagy in Liver Physiology and Liver Diseases, International Journal of Molecular Sciences, Jan, 2019, 20(2): 300.
  11. Ke PY, The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions. International Journal of Molecular Sciences, Dec, 2018, 19(12): 3940.
  12. Lai JH, Wang MY, Huang CY, Wu CH, Hung LF, Yang CY, Ke PY, Luo SF, Liu SJ, Ho LJ, Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells, EMBO Reports, Aug, 2018, 19(8): e46182.
  13. Liang KH, Ahn SH, Lee HW, Huang YH, Chien RN, Hu TH, Lin KH, Yeh CS, Hsu CW, Lin CL, Pan TL, Ke PY, Chang ML, Yeh CT, A novel risk score for hepatocellular carcinoma in Asian cirrhotic patients: a multicentre prospective cohort study, Scientific Reports, Jun, 2018, 8(1): 8608.
  14. Lin CL, Chien RN, Liang KH, Ke PY, Huang YH, Yeh CT, Intrahepatic HCV RNA Level and Genotype 1 Independently Associate with Hepatic Reticulon 3 Expression, Anticancer Research, Jun, 2017, 37(6): 2885-2891.
  15. Ke PY, Horning cell self-digestion: Autophagy wins the 2016 Nobel Prize in Physiology or Medicine, Biomedical Journal, Feb, 2017, 40(1): 5-8.
  16. Huang YH, Liang KH, Chien RN, Hu TH, Lin KH, Hsu CW, Lin CL, Pan TL, Ke PY, Yeh CT, A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients. Scientific Reports, Mar, 2017, 7(1): 523.
  17. Klionsky DJ et al, and Ke PY, and 1296 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd Edition), Autophagy, Jan, 2016, 12(1): 1-222.
  18. Wu MJ, Ke PY, Horng JT, RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication, Biochemical and Biophysical Research Communications, Nov, 2014, 454(1): 19-24.
  19. Wu MJ, Ke PY, Hsu JT, Yeh CT, and Horng JT, Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction, Cellular Microbiology, Nov, 2014, 16(11): 1603-1618.
  20. Ke PY, Chen SS, Autophagy in hepatitis C virus-host interactions: Potential roles and therapeutic targets for liver-associated diseases, World Journal of Gastroenterology, May, 2014, 20(19): 5773-5793.
  21. Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, Chen CY, Lin Y H, and Lin KH, Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism, Autophagy, Jan, 2014, 10(1): 20-31.
  22. Ke PY, Chen SS, Active RNA replication of hepatitis C virus downregulates CD81 expression, PLoS ONE, Jan, 2013, 8(5): e54866.
  23. Ke PY, Chen SS, Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases, Viruses, Oct, 2012, 4(10): 2251-2290.
  24. Klionsky DJ et al, and Ke PY, and 1296 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (2nd Edition), Autophagy, Apr, 2012, 8(4):445-544.
  25. Ke PY, Chen SS, Autophagy: a novel guardian of HCV against innate immune response, Autophagy, May, 2011, 7(5): 533-535.
  26. Ke PY, Chen SS, Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro, Journal of Clinical Investigation, Jan, 2011, 121(1): 37-56.
  27. Chen SS, Yang P, Ke PY, Li HF, Chan WE, Chang DK, Chuang CK, Tsai Y, Huang SC, Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection, Journal of Virology, Jan, 2009, 83(2): 870-883.
  28. Ke PY, Hu CM, Chang YC, Chang ZF, Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding, FASEB Journal, Apr, 2007, 21(4): 1276-1284.
  29. Ke PY, Kuo YY, Hu CM, Chang ZF, Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability, Genes & Development, Aug, 2005, 19(16): 1920-1933.
  30. Ke PY, Chang ZF, Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway, Molecular and Cellular Biology, Jan, 2004, 24(2): 514-526.
  31. Li CL, Lu CY, Ke PY, Chang ZF, Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site, Biochemical and Biophysical Research Communications, Jan, 2004, 313(3): 587-593.
  32. Ke PY, Yang CC, Tsai IC, Chang ZF, Degradation of human thymidine kinase is dependent on serine-13 phosphorylation: involvement of the SCF-mediated pathway, Biochemical Journal, Feb, 2003, 370(Pt 1): 265-273.

BOOK CHAPTERS

  1. Chen SS and Ke PY, Suppression of innate antiviral immunity after hepatitis C virus infection: role of the unfolded protein response and autophagy. 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. Ke PY and Chen SS, Multifaceted Roles of Autophagy in the Life Cycle of Flaviviridae. Recent Research Developments in Virology, Vol. 8. Chapter 1. (ISBN: 978-81-7895-563-6). Kerala, India: Transworld Research Network. Apr, 2012.

 

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