移至主內容

闕斌如

闕斌如
教授
美國普渡大學博士
生科大樓11樓1127室/腫瘤生化機制研究室
(04)22840896#120
pjchueh@dragon.nchu.edu.tw

研究領域

我們在1995年美國國家科學院院刊 (The Proceedings of the National Academy of Sciences of the United States of America, PNAS)中,首度發表辣椒素有效的抑制tNOX腫瘤蛋白的活性,並發現這樣的活性被抑制後,導致腫瘤細胞的凋亡及細胞生長的降低;而辣椒素對非癌化的細胞則無明顯的影響。tNOX腫瘤蛋白為一NADH氧化酶酵素,其活性及蛋白表現與腫瘤細胞的生長與存活能力有重要的關係,我們也在癌症病人的血清之中偵測到tNOX腫瘤蛋白的活性及蛋白表現,但在非癌化的細胞或非癌症病人的血清之中,則只有相對低量的tNOX 蛋白。後續以RNA干擾技術的方式,將基因靜默進而達到使tNOX蛋白質的表現量降低,我們發現tNOX蛋白表現量與細胞的增生與細胞移動能力有正向的關係;反之,當tNOX蛋白被刺激增加或大量表現時,細胞的侵犯性也隨之增加並伴隨著 EMT使細胞驅向癌化。目前我們認為tNOX腫瘤蛋白之所以可以參與細胞內許多功能的調控,主要是因為其NADH氧化酶的酵素能力,影響細胞內NAD+NADH的濃度比率,進而調節去乙烯基酶SIRT1 的酵素能力,而SIRT1將其他蛋白質去乙烯基後所可影響細胞能量代謝及老化等。目前,實驗室的研究領域主要可以分成下列幾大方向

1.以細胞株模式及動物實驗探討tNOX 腫瘤蛋白及其所調控的SIRT1 在癌症發展所扮演的角色,如細胞週期、細胞死亡及細胞移動等生物功能之調控。
2. tNOX 腫瘤蛋白SIRT1之間相互的調控機制。 
3. 抑癌藥物所引發細胞凋亡及細胞自噬機制之探討。
4. 奈米物質的細胞毒性及其引發毒性機制之探討。

教授科目

上學期-醫用生物技術() (2學分)

上學期-細胞死亡之分子機制特論(2學分)

上學期-氧化還原酶蛋白功能特論(2學分)

上學期-蛋白結構及功能(2學分)

下學期-細胞増生之分子機制特論(2學分)

下學期-醫用生物技術() (2學分)

下學期-氧化酶蛋白與疾病特論(2學分)

全學年-NADH氧化酶蛋白功能分析研究(6學分)

簡要經歷

教授-國立中興大學生物醫學研究所 (2/2013-迄今)
國際處學術交流組組長-國立中興大學 (9/2010-5/2014)

副教授-國立中興大學生物醫學研究所 (2/2009-1/2013)
助理教授-國立中興大學生物醫學研究所-(2/2005-1/2009) 
助理教授-中山醫學大學生命科學系-(9/2003-2/2005) 
助理研究員-美國普渡大學藥物化學暨分子藥理研究所-(Purdue University)(10/2001-8/2003)
博士後研究員-美國普渡大學藥物化學暨分子藥理研究所 (Purdue University)(3/1998-9/2001)
博士-美國普渡大學-(1/1994-12/1997)
碩士-國立中興大學化學研究所 (9/1989-6/1991)
學士-國立中興大學化學系 (9/1986-6/1989)

獲獎項目

擔任國際學術期刊評審委員: SCI期刊審查
Advanced Healthcare Materials
Biochemistry and Cell Biology
Biochimie
Bioresource Technology
Biotechnology Advances

Cancer Biology & Therapy
Cancer Immunology Immunotherapy
Chemosphere

Chinese Journal of Physiology
Colloids and Surfaces B: Biointerfaces
 
Enzyme and Microbial Technology
Experimental Cell Research
International Journal of Molecular Sciences
Investigational New Drugs
Journal of Agricultural and Food Chemistry
Journal of Cellular Physiology
Journal of Dietary Supplements
Journal of Hazardous Materials
Journal of Nanoparticle Research
Molecular and Cellular Biochemistry
Molecular Membrane Biology
Nanomedicine

Plos One
Process Biochemistry
Toxicology Letters

學術著作

A.期刊論文

  1. Lin, M.H., Lee, Y.H., Cheng, H.L., Chen, H.Y., Jhuang, F.H., Chueh, P.J.* (2016) Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1). Molecules 21(7): pii: E849
  2. Hung Yen Chen, Yi-Hui Lee, Huei Yu Chen, Chia An Yeh, Pin Ju Chueh, and Yi-Mei J. Lin* (2016) Capsaicin-inhibited aggressive phenotypes is through downregulation of tumor-associated NADH oxidase (tNOX) by POU domain transcription factor BRN2. Molecules 21(6): pii: E733
  3. Wu, C.C., Cheng, C.H., Lee, Y.H., Chang, I.L., Chen, H.Y., Hsieh, C.P., Chueh, P.J.*  (2016) Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway. J Agric Food Chem. 64(21):4220-6
  4. Cheng, H.L., Lee, Y.H., Yuan, T.M., Chen, S.W., Chueh, P.J.* (2016) Update on a tumor-associated NADH oxidase in gastric cancer cell growth. World J Gastroenterol. 22(10):2900-5 
  5. Tikhomirov, A.S., Shchekotikhin, A.E., Lee, Y.H., Chen, Y.A., Yeh, C.A., Tatarskiy, V.V. Jr, Dezhenkova, L.G., Glazunova, V.A., Balzarini, J., Shtil, A.A., Preobrazhenskaya, M.N., Chueh, P.J.* (2015) Synthesis and Characterization of 4,11-Diaminoanthra[2,3-b]furan-5,10-diones: Tumor Cell Apoptosis through tNOX-Modulated NAD(+)/NADH Ratio and SIRT1. J Med Chem. 58(24):9522-34. 
  6. Lee, Y.H., Chen, H.Y., Su, L.J., Chueh, P.J.* (2015) Sirtuin 1 (SIRT1) deacetylase activity and NAD+/NADH ratio are imperative for capsaicin-mediated programmed cell death. J Agric Food Chem. 63, 7361-70.
  7. Liang, R.Y., Tu, H.F., Tan, X.T., Yeh, Y.S., Chueh, P.J., Chuang, S.M.* (2015) A gene signature for gold nanoparticle exposed human cell lines. Toxicol Res. 4, 365-375.
  8. Yuan, T.M., Liang, R.Y., Chueh, P.J., Chuang, S.M.* (2015) Role of ribophorin II in the response to anticancer drugs in gastric cancer cell lines. Oncol Lett. 9, 1861-1868.
  9. Kumar, K.J., Vani, M.G., Chueh, P.J., Mau, J.L., Wang, S.Y.* (2015) Antrodin C inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via suppression of Smad2/3 and β-catenin signaling pathways. PLoS One 10(2):e0117111.
  10. Chueh, P.J., Liang, R.Y., Lee, Y.H., Zeng, Z.M., Chuang, S.M.* (2014) Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines. J Hazard Mater. 264, 303-312.
  11. Chuang SM, Lee YH, Liang RY, Roam GD, Zeng ZM, Tu HF, Wang SK, Chueh, P.J.* (2013) Extensive evaluations of the cytotoxic effects of gold nanoparticles. Biochim Biophys Acta. 1830(10):4960-73.
  12. Su, Y.C., Lin, Y.H., Zeng, Z.H., Shao, K.N., Chueh, P.J.* (2012) Chemotherapeutic agents enhance cell migration and epithelial-to-mesenchymal transition through transient up-regulation of tNOX (ENOX2) protein. Biochimica et Biophysica Acta- General Subjects 1820(11):1744-52.
  13. Zeng, Z.H., Chuang, S.M., Chang, T.C., Hong, C.W., Chou, J.C., Yang, J.J., Chueh, P.J.*, “(2012) Phosphorylation of serine-504 of tNOX (ENOX2) modulates cell proliferation and migration in cancer cells.,” Exp. Cell Res., vol.318, pp.1759-1766., 07 2012.
  14. Liu, N.C., Hsieh, P.F., Hsieh, M.K., Zeng, Z.M., Cheng, H.L., Liao, J.W., Chueh, P.J.*, “(2012) Capsaicin-Mediated tNOX (ENOX2) Up-regulation Enhances Cell Proliferation and Migration in Vitro and in Vivo.,” J Agric Food Chem., vol.60., pp.2758-2765, 01 2012.
  15. Wang, H.M., Chuang, S.M., Su, Y.C., Li, Y.H., Chueh, P.J.* , “(2011) Down-Regulation of Tumor-Associated NADH Oxidase, tNOX (ENOX2), Enhances Capsaicin-Induced Inhibition of Gastric Cancer Cell Growth. ,” Cell Biochem Biophys., vol.61, pp.355-366, 01 2011.
  16. Shen, Y.H., Chen, B.R., Cherng, S.H., Chueh, P.J., Tan, X., Lin, Y.W., Lin, J.C., Chuang, S.M., “(2011) Cisplatin transiently up-regulates hHR23 expression through enhanced translational efficiency in A549 adenocarcinoma cells. ,” Toxicol Lett. , vol.205(3), pp.341-350., 01 2011.
  17. Cheng, W.L., Lin, T.Y., Tseng, Y.H., Chu, F.H., Chueh, P.J., Kuo, Y.H., Wang, S.Y., “(2011) Inhibitory effect of human breast cancer cell proliferation via p21-mediated G1 cell cycle arrest by araliadiol isolated from Aralia cordata Thunb,” Planta Med. , vol.77(2):, pp.164-8, 01 2011.
  18. Tang, X., Chueh, P.J., Jiang, Z., Layman, S., Martin, B., Kim, C., Morré, D.M., Morré, D.J., “(2010) Essential role of copper in the activity and regular periodicity of a recombinant, tumor-associated, cell surface, growth-related and time-keeping hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ENOX2),” J Bioenerg Biomembr. , vol.42, pp.355-60, 01 2010.
  19. Kuo, Y.F., Su, Y.Z., Tseng, Y.H., Wang, H.M., Chueh, P.J.* , “(2010) Flavokawain B, A novel chalcone, from Alpinia pricei Hayata with potent apoptotic activity: involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells,” Free Radic. Biol. Med. 49(2), pp.214-226, 01 2010.
  20. Huang, S., Chueh, P.J., Lin, Y.W., Shih, T.S., Chuang, S.M., “(2009) Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-exposure,” Toxicol Appl Pharmacol. 241(2), pp.182-94, 01 2009.
  21. Wang, H.M., Chueh, P.J., Chang, S.P., Yang, C.L., Shao, K.N., “(2009) Effect of capsaicin on tNOX (ENOX2) protein expression in stomach cancer cells,” BioFactors 34(3):, pp.209-17, 01 2009.
  22. Mao, L.C., Wang, H.M., Lin, Y.Y., Chang, T.K., Hsin, Y.H., Chueh, P.J.* , “(2008) Stress-induced downregulation of tumor-associated NADH oxidase during apoptosis in transformed cells,” FEBS Lett. 582(23), pp.3445-3450, 01 2008.
  23. Hsin, Y.H., Chen, C.F., Huang, S., Shih, T.S., Lai, P.S., Chueh, P.J.*, “(2008) The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells,” Toxicol. Lett. 179(3), pp.130-139, 01 2008.
  24. Liu, S.C., Yang, J.J., Shao, K.N., Chueh, P.J.*, “(2008) RNA interference targeting tNOX attenuates cell migration via a mechanism that involved membrane association of Rac,” Biochem. Biophys. Res. Commun. 365(4), pp.672-677, 01 2008.
  25. Lin, C.T., Chu, F.H., Chang, S.T., Chueh, P.J., Su, Y.C., Wu, K.T., Wang, S.Y., “(2007) Secoaggregatalactone-A from Lindera aggregata Induces Apoptosis in Human Hepatoma Hep G2 cells,” Planta Med. 73(15), pp.1548-1553, 01 2007.
  26. Tang, X., Tain, Z., Chueh, P.J., Chen, S., Morré, D.M., and Morré, D.J. , “(2007) Alternative Splicing as the Basis for Specific Localization of tNOX, a Unique Hydroquinone (NADH) Oxidase, to the Cancer Cell Surface,” Biochemistry. 46(43), pp.12337-12346, 01 2007.
  27. Morré, D.J., Chueh, P.J., Yagiz, K., Balicki, A., Kim, C., and Morré, D.M., “(2007) ECTO-NOX target for the anticancer isoflavene phenoxodiol,” Oncology Research 16 (7), pp.299-312, 01 2007.
  28. Chen, C.F., Huang, S., Liu, S. C. and Chueh, P. J.*, “(2006) Effect of polyclonal antisera to recombinant tNOX protein on the growth of transformed cells,” BioFactors , vol.28(2), pp.119-133, 01 2006.
  29. Chueh, P.J.*, Wu, L.Y., Morré, D.M. and Morré, D.J., “(2004) tNOX is both necessary and sufficient as a cellular target for the anticancer actions of capsaicin and the green tea catechin (-)-epigallocatechin-3-gallate,” BioFactors , vol.20(4), pp.249-263, 01 2004.
  30. Huang, C.Y., Chueh, P.J.*, Tseng, C.T., Liu, K.Y., Tsai, H.Y., Kuo, W.W., Chou, M.Y., and Yang, J.J., “(2004) ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells,” Biochem Biophys Res Commun. , vol.324(3), pp.973-980, 01 2004.
  31. Huang, C.Y., Kuo, W.W., Chueh, P.J., Tseng, C.T., Chou, M.Y., and Yang, J.J., “(2004) Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK,” Biochem Biophys Res Commun. , vol.324(1), pp. 424-431, 01 2004.
  32. Chueh, P.J.*, Kim, C., Morré, D.M. and Morré, D.J., “(2002) Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface,” Biochemistry, vol. 41(11), pp. 3732-3741, 01 2002.
  33. Chueh, P.J.*, Morre, D.M., Morre, D.J., “ (2002) A site-directed mutagenesis analysis of tNOX functional domains,” Biochim Biophys Acta. , vol.1594(1), pp.74-83, 01 2002.
  34. Morré, D.J., Chueh, P.J., Pletcher, J., Tang, X., Wu, L.Y., Morré, D.M., “(2002) Biochemical basis for the biological clock,” Biochemistry, vol. 41(40), pp.11941-11945, 01 2002.
  35. Cho, N., Chueh, P.J., Caldwell, S., Morré, D.M. and Morré, D.J., “(2002) Monoclonal antibody to a cancer-specific and drug-responsive hydroquinone (NADH) oxidase from the sera of cancer patients,” Cancer Immunology & Immunotherapy , vol.51(3), pp.121-129, 01 2002.
  36. Morré, D.J., Sedlak, D., Tang, X., Chueh, P.J., Geng, T., Morré, D.M., “(2001) Surface NADH oxidase of HeLa cells lacks intrinsic membrane binding motifs,” Arch Biochem. Biophys. , vol.392(2), pp.251-256, 01 2001.
  37. Kelker, M., Kim, C., Chueh, P.J., Guimont, R., Morré, D.M., Morré, D.J. , “(2001) Cancer isoform of a tumor-associated cell surface NADH oxidase (tNOX) has properties of a prion,” Biochemistry, vol. 40(25), pp.7351-7354, 01 2001.
  38. Chueh, P. J.* , “(2000) Cell membrane redox system and transformation,” Antioxidants and Redox signaling [Review] , vol.2(2), pp.177-187, 01 2000.
  39. del Castillo-Olivares, A., Yantiri, F., Chueh, P.J., Wang, S., Sweeting, M., Sedlak, D., Morré, D.M., Burgess, J., and Morré, D.J., “(1998) A drug-responsive and protease-resistant 34 kD NADH oxidase from the surface of HeLa S cell,” Arch. Biochem. Biophys. , vol.358(1), pp.125-140, 01 1998.
  40. Morré, D.J., Chueh, P.J., Lawler, J. and Morré, D.M., “(1998) The sulfonylurea-inhibited NADH oxidase activity of HeLa cell plasma membranes has properties of a protein disulfide-thiol oxido-reductase with protein disulfide-thiol interchange activity,” J. Bioenerg. Biomemb. , vol.30(5), pp.477-487, 01 1998.
  41. Morré, D.M., Wang, S., Chueh, P.J., Lawler, J., Safranski, K., Jacobs, E. and Morré, D.J., “(1998) A molecular basis for retinol stimulation of vesicle budding in vivo and in vitro.,” Mol. Cell. Biochem. , vol.187(1-2), pp.73-83, 01 1998.
  42. Yantri, F., Morré, D.J., Yagiz, K., Barogi, S., Wang, S., Chueh, P.J., Cho, N., Sedlak, D. and Morré, D.M. , “(1998) Capsaicin-responsive NADH oxidase activities from urine of cancer patients.,” Arch. Biochem. Biophys. , vol.358(2), pp.336-342, 01 1998.
  43. Chueh, P.J.*, Morré, D.J., Wilkinson, F.E., Gibson, J., and Morré, D.M., “(1997) A 33.5 kD heat- and protease-resistant NADH oxidase inhibited by capsaicin from sera of cancer patients,” Arch. Biochem. Biophys. , vol.342(1), pp.38-47, 01 1997.
  44. Chueh, P.J.*, Morré, D.M., Penel, C., DeHann, T., and Morré, D.J., “(1997) The hormone-responsive NADH oxidase of the plant plasma membrane has properties of a NADH,” protein disulfide reductase. J. Biol. Chem. , vol.272(17), pp.11221-11227, 01 1997.
  45. Wilkinson, F., Kim, C., Cho, N., Chueh, P.J., Leslie, S., Moya-Camarena, S., Wu, L.Y., Morré, D.M., and Morré, D.J., “(1996) Isolation and identification of a capsaicin-inhibited NADH oxidase activity of culture media conditioned by growth of HeLa cells,” Arch. Biochem. Biophys. , vol.336(2), pp.275-282, 01 1996.
  46. Morré, D.J., Chueh, P.J., and Morré, D.M., “(1995) Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture. Proc,” Natl. Acad. Sci. U.S.A. , vol.92(6), pp.1831-1835, 01 1995.

    B.研討會論文

    C.專書

    Chueh, P.J. (2013) The cancer-suppressing and -promoting actions of capsaicin. In Role of Capsaicin in Oxidative Stress and Cancer. Editor Sunil Padman K.P. Springer Science (Ch 7, pp. 131-147).

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