91猫先生

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生化暨分子生物学科

生化暨分子生物学科

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柯博元

职称：副教授

研究室名称：细胞压力反应之分子机制研究室

最高学歷：博士

学校/国家：国立台湾大学医学院/台湾

分机号码：5115

电子邮件帐号：?pyke0324@mail.cgu.edu.tw

研究室现有：博士班研究生??1?人，?硕士班研究生?1人，专任研究助理??1?人，大学部专题生? 5?人，Update：2022/08/04?

研究方向及研究室特色：

细胞自噬作用(Autophagy)是一种经由细胞遭遇压力(如营养缺乏)所引发的一种细胞反应，自噬作用藉由细胞内膜构造的重组以及一连串讯息传递而产生前自噬体(preautophagosome)，再形成双层膜构造(Isolation membrane/phagophore)，藉由此双层膜结构包覆细胞质成為自噬体(autophagosome)，随之自噬體便與溶小體結合為溶自噬体(autolysosome)，將其包覆之內含物分解。细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，研究细胞自噬作用對於了解細胞如何拮抗细胞所面临压力至為重要。本研究室未来有下列几个方向:

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(1)???????许多病毒的感染被發現會引起细胞自噬作用以促進病毒的複製，以C型肝炎為例，我们过去的研究(Journal of Clinical Investigation, 2011),?发现病毒感染宿主细胞会经由不正常蛋白质堆叠反应(unfolded protein response)引发自噬作用，而自噬作用则透过抑制即时性抗病毒免疫力的活化来促进病毒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讨细胞自噬作用如何透過調節调控即时性免疫反应讯息传递或是分子的运输以抑制抗病毒免疫反应的活化。

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(2)???????许多病毒所引发之自噬作用多半透过不正常蛋白质堆叠反应而活化，截至目前為止，其详细的分子机制依然不清楚；目前的研究显示，由於病毒大多於内质网(endoplasmic reticulum)所形成的膜狀构造进行复製而产生的内质网压力(endoplasmic reticulum stress)，因而诱发不正常蛋白质堆叠反应，再进而活化细胞自噬作用，本研究室将来将利用干扰性RNA以及转录基因体学的方法来探讨究竟是什麼样的分子在不正常蛋白质堆叠所引发的细胞自噬作用扮演重要的角色，而其透过的是什麼样的分子机制，包括，基因转录、蛋白质新合成或是蛋白质转录后修饰等。

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(3)???????细胞自噬作用对於癌细胞发生及演进既是促进者也是抑制者的角色，目前对於自噬作用在癌症形成的过程其确切角色的相关研究结论依旧是混沌不清的，因此本研究室将对细胞自噬作用在国人常见的肝癌发生过程中扮演的功能角色进行探讨。

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Current position:

Assistant Professor

Department of Biochemistry & Molecular Biology and Graduate Institute of Biomedical Sciences, College of Medicine, 91猫先生, 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

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HONORS & ACADEMIC SERVICE

(I) AWARDS

  1. 全球前?2%?顶尖科学家(World’s Top 2% Scientists) 获奖人(2021).
  2. 长庚大学108年度優良教师獎(2019)
  3. 科技部杰出学者养成计画 (MOST grant award for cultivation of outstanding young scholars，支持105~108叁年期研究计画)获奖人
  4. 国家衛生研究院 (NHRI)103年度Career Development Grant (CDG，支持103-107四年期研究计画)获奖人
  5. 科技部补助大专校院奖励特殊优秀人才(2015)
  6. 科技部补助大专校院奖励特殊优秀人才(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. 探索专一性粒腺体自噬作用在黄热病毒与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), 补助机构: 科技部
  2. 探讨人类DEAD-box helicase 3所導引之细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), 补助机构: 科技部
  3. 專一细胞自噬反應引發之選擇性分解作用於调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), 补助机构: 科技部
  4. 探索C型肝炎病毒引發之專一選擇性细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), 补助机构: 国家衛生研究院
  5. 细胞自噬分解作用於負向调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), 补助机构: 科技部
  6. 探讨selective autophagy调控RLR抗病毒讯息传递之分子机转, (MOST 101-2320-B-182-043) (2012/8/1~2013/7/31) (NT$ 1,050,000), 补助机构: 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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