研究領域與專長

本實驗室的研究工作著重於以下兩個方向:

一. 一氧化氮保護心血管系統免於缺血性病變的傷害: 來自臨床的觀察早已指出,在缺血性心肌梗塞發生時,缺氧及缺氧後重新的血流供應,皆會造成心臟組織嚴重的損壞。最近的研究進一步顯示,具訊息功能的小分子一氧化氮能夠保護心臟組織,避免上述的傷害;因此,若能尋找到提升心臟組織周邊一氧化氮濃度的方法,將對缺血性心肌梗塞的治療上提供具體的幫助。眾多文獻顯示亞硝酸鹽能夠發揮類似一氧化氮的功能,讓心肌組織在缺氧及缺氧後重新的血流供應的情況下維持較好的存活率。根據這樣的觀察,進一步的研究提出許多假設,試圖解釋亞硝酸鹽所扮演的角色。當缺血性心肌梗塞發生時,心臟組織周邊處於低氧的環境,此時局部紅血球中的血紅素有能力將亞硝酸鹽還原為一氧化氮;若一氧化氮能夠穿透紅血球的細胞膜,則此一來自紅血球的一氧化氮就有機會進入周邊的心臟組織,發揮其保護心肌細胞的功能。另一方面,若亞硝酸鹽能直接進入心肌細胞,並透過心肌細胞內生性的酵素將之還原成一氧化氮,亦可發揮其保護功能。本研究的重點,即在於釐清亞硝酸鹽如何透過紅血球中的血紅素,或是心肌細胞內生性的酵素而還原成具有高度活性的一氧化氮,進而保護心臟組織,避免缺血性心肌梗塞造成不可逆的嚴重傷害。我們將採用細胞模式進行機制性的研究,將亞硝酸鹽的還原過程、一氧化氮輸送出紅血球的過程、以及一氧化氮在心肌細胞中促進存活的原因一一釐清。我們並將研究重要訊息分子在這些過程中扮演的角色,以期協助尋找亞硝酸鹽或一氧化氮的標靶。我們預期此一研究成果將對缺血性心肌梗塞的治療策略提供新穎的思考與設計。

二. 蛋白質磷酸化與去磷酸化調控細胞骨架的機制: 過去二十年的研究成果早已指出蛋白質磷酸化的重要性。此種後轉譯修飾作用受到蛋白激酶 kinase及磷酸水解酶 phosphatase之嚴密調控,並扮演極為重要的生理功能。 在本研究中,我們將探討蛋白激酶及磷酸水解酶如何參與細胞骨架蛋白actin重組之過程。我們先前的研究工作已經證實果蠅所表現的骨架蛋白調控分子Kette是一磷酸化的蛋白質,而Kette又可受到磷酸水解酶PTP61F及蛋白激酶dAbl的調控,此時細胞內骨架蛋白Actin的重組則因Kette磷酸化的程度有所快速的變遷,此一重要的發現將作為本計畫的基礎。在後續實驗中,我們將首先釐清Kette、PTP61F及dAbl三者間的關係,並以發育中的果蠅為模式,探討此一調控對Actin參與果蠅器官塑型的重要性。另外,我們將逐一探討其他相關的果蠅骨架蛋白調控分子,包括SCAR/WAVE、Sra-1、Abi,進而瞭解這些分子如何與PTP61F 及dAbl互動,並共同調控果蠅細胞骨架蛋白actin的重組。基於演化上的保守性,類似的機制可能存在於哺乳動物細胞中;因此,我們也將探討蛋白激酶及磷酸水解酶如何透過影響骨架蛋白調控分子的磷酸化程度,進而促成哺乳動物細胞骨架蛋白Actin的快速重組。目前我們將重點放在人類磷酸水解酶PTP1B及蛋白激酶c-Abl針對蛋白調控分子NAP-1的磷酸化所進行的調整。整體而言,此一新穎的研究方向將有助於釐清蛋白質磷酸化及骨架蛋白調控之間的互動關係。

學經歷
經歷
  • 2014 – 迄今   研究員, 中央研究院生物化學研究所
  • 2017 – 2019   代理副所長, 中央研究院生物化學研究所
  • 2008 – 2014   副研究員, 中央研究院生物化學研究所
  • 2003 – 2008   助研究員, 中央研究院生物化學研究所
  • 1999 – 2003   博士後研究員, 美國紐約州冷泉港實驗室
學歷
  • 1995 – 1999   博士, 生化及分子生物, 美國內布拉斯加州立大學醫學中心
  • 1992 – 1994   碩士, 毒理學, 臺灣大學醫學院
  • 1985 – 1989   學士, 農業化學, 臺灣大學農學院
主要著作
Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD*, Haj FG*, and Meng TC*
Free Rad Biol Med (2016)
Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC*, Wang AH*
Structure (2015)
Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC* Meng TC*
Mol. Cell. Biol. (2014)
Pan KT, Chen YY, Pu TH, Chao YS, Yang CY, Bomgarden RD, Rogers JC, Meng TC*, Khoo KH*
Antioxidant and Redox Signaling (2014)
Chen KE, Lin SY, Wu MJ, Ho MR, Santhanam A, Chou CC, Meng TC*, Wang AH*
Science Signaling (2014)
Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, Meng TC
Circulation research (2011)
Ku HY, Wu CL, Rabinow L, Chen GC, Meng TC
Molecular and Cellular Biology (2009)
Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC
J. Biol. Chem. (2008)
Chang YC, Lin SY, Liang SY, Pan KT, Chou CC, Chen CH, Liao CL, Khoo KH, Meng TC
Journal of Proteome Research (2008)
M. Halle, Y. C. Liu, S. Hardy, J. F. Theberge, C. Blanchetot, A. Bourdeau, T. C. Meng and M. L. Tremblay
Mol Cell Biol (2007)
著作列表
  1. Yang CF, Lin TJ, Liu CH, Chen YC, Tang SC, Yang JH, (Meng TC)*, Cheng CF*  (2020-10)  Nutrition  78, 110892  "Eating right for a healthier heart: Food choice contributes to cardiometabolic benefits and reduction of carotid intima-media thickness."
  2. Yang CF, Chen YY, Singh JP, Hsu SF, Liu YW, Yang CY, Chang CW, Chen SN, Shih RH, Hsu SD, Jou YS, Cheng CF, (Meng TC)  (2020-04)  Cardiovascular research  116(5), 1032-1046  "Targeting Protein Tyrosine Phosphatase PTP-PEST for Therapeutic Intervention in Acute Myocardial Infarction."
  3. Chen YJ, Liu YC, Liu YW, Lee YB, Huang HC, Chen YY, Shih YH, Lee YC, Cheng CF, (Meng TC)  (2019-07)  Antioxidants & redox signaling  31(2), 109-126  "Nitrite Protects Neurons Against Hypoxic Damage Through S-nitrosylation of Caspase-6."
  4. Bottini A, Wu DJ, Ai R, Le Roux M, Bartok B, Bombardieri M, Doody KM, Zhang V, Sacchetti C, Zoccheddu M, Lonic A, Li X, Boyle DL, Hammaker D, (Meng TC), Liu L, Corr M, Stanford SM, Lewis M, Wang W, Firestein GS, Khew-Goodall Y, Pitzalis C, Bottini N  (2019-05)  Annals of the rheumatic diseases  78(5), 600-609  "PTPN14 phosphatase and YAP promote TGF beta signalling in rheumatoid synoviocytes."
  5. Hsu SF, Lee YB, Lee YC, Chung AL, Apaya MK, Shyur LF, Cheng CF, Ho FM, (Meng TC)  (2018-05)  The FEBS journal  285(9), 1593-1610  "Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1."
  6. Willoughby LF, Manent J, Allan K, Lee H, Portela M, Wiede F, Warr C, (Meng TC), Tiganis T, Richardson HE  (2017-07)  The FEBS journal  284(14), 2231-2250  "Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants."
  7. Huang YJ, Yang CK, Wei PL, Huynh TT, Whang-Peng J, (Meng TC), Hsiao M, Tzeng YM, Wu AT, Yen Y  (2017-02)  Journal of hematology & oncology  10(1), 60  "Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways."
  8. Huang YJ, Th Wu A, Chiou HY, Chuang MT, (Meng TC), Chien LN, Yen Y  (2017-01)  Oncotarget  8(4), 6642-6651  "Interactive role of diabetes mellitus and female sex in the risk of cholangiocarcinoma: A population-based nested case-control study."
  9. Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD, Haj FG, (Meng TC)  (2016-10)  Free Radical Biology and Medicine  99, 199-213  "S-Nitrosylation of Endogenous Protein Tyrosine Phosphatases in Endothelial Insulin Signaling"
  10. Li MY, Lai PL, Chou YT, Chi AP, Mi YZ, Khoo KH, Chang GD, Wu CW, (Meng TC), Chen GC  (2015-07)  Oncogene  34(29), 3791-3803  "Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation."
  11. Hatzihristidis T, Desai N, Hutchins AP, (Meng TC), Tremblay ML, Miranda-Saavedra D  (2015-04)  FEBS letters  589(9), 951-966  "A Drosophila-centric view of protein tyrosine phosphatases."
  12. Chen KE, Li MY, Chou CC, Ho MR, Chen GC, (Meng TC), Wang AH  (2015-04)  Structure  23(4), 653-664  "Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases."
  13. Tchankouo-Nguetcheu S, Udinotti M, Durand M, (Meng TC), Taouis M, Rabinow L  (2014-10)  Molecular genetics and genomics  289(5), 795-806  "Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B."
  14. Kai-En Chen, Shu-Yu Lin, Mei-Ju Wu, Meng-Ru Ho, Abirami Santhanam, Chia-Cheng Chou, (Tzu-Ching Meng), and Andrew H. -J. Wang  (2014-10)  Science Signaling  7(347), ra98  "Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain–modulated complex formation"
  15. Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC, (Meng TC)  (2014-05)  Molecular and cellular biology  34(9), 1594-1606  "Ecdysone-induced receptor tyrosine phosphatase PTP52F regulates Drosophila midgut histolysis by enhancement of autophagy and apoptosis."
  16. Pan KT, Chen YY, Pu TH, Chao YS, Yang CY, Bomgarden RD, Rogers JC, (Meng TC), Khoo KH  (2014-03)  ANTIOXIDANTS & REDOX SIGNALING  20(9), 1365-1381  "Mass Spectrometry-Based Quantitative Proteomics for Dissecting Multiplexed Redox Cysteine Modifications in Nitric Oxide-Protected Cardiomyocyte Under Hypoxia."
  17. Chang YC, Tang HW, Liang SY, Pu TH, (Meng TC), Khoo KH, Chen GC  (2013-05)  Journal of proteome research  12(5), 2138-2150  "Evaluation of Drosophila metabolic labeling strategies for in vivo quantitative proteomic analyses with applications to early pupa formation and amino acid starvation."
  18. Buszard BJ, Johnson TK, (Meng TC), Burke R, Warr CG, Tiganis T  (2013-04)  Molecular and cellular biology  33(7), 1345-1356  "The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine phosphatase 61F regulate Drosophila growth, life span, and fecundity."
  19. Santhanam A, Liang SY, Chen DY, Chen GC*, (Meng TC)*  (2013-01)  The FEBS journal  280(2), 476-488  "Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition."
  20. Chen DY, Li MY, Wu SY, Lin YL, Tsai SP, Lai PL, Lin YT, Kuo JC, (Meng TC), Chen GC  (2012)  Journal of cell science  125(20), 4841-4852.  "The Bro1 domain-containing Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration."
  21. Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, (Meng TC)  (2011-12)  Circulation research  109,1375-1386  "Nitrite-Mediated S-Nitrosylation of Caspase-3 Prevents Hypoxia-Induced Endothelial Barrier Dysfunction."
  22. Wu CL, Buszard B, Teng CH, Chen WL, Warr C, Tiganis T, (Meng TC)  (2011-10)  Biochemical journal  439(1), 151-159  "Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signaling."
  23. Yu-Chiang Chao, Shih-De Yeh, Hsiao-Wen Zan, Gao-Fong Chang, Hsin-Fei Meng, Chen-Hsiung Hung, (Tzu-Ching Meng)  (2011-05)  ORGANIC ELECTRONICS  12(5), 751-755  "Integrated semiconductor optoelectronic devices for real-time and indicator-free detection of aqueous nitric oxide."
  24. Chao Y.C., Yeh S.D., Zan H.W., Hong Y.R., Wu M.C., Chang G.F., Tsai P.Y., Meng H.F., Hung C.H., (Meng T.C.), Hsu C.S., and Horng S.F.  (2010-06)  APPLIED PHYSICS LETTERS  96, 223702(1-3)  "Real-time and indicator-free detection of aqueous nitric oxide with hydrogel film."
  25. Hsu MF, (Meng TC)  (2010-03)  JOURNAL OF BIOLOGICAL CHEMISTRY  285(11), 7919-7928  "Enhancement of insulin responsiveness by nitric oxide-mediated inactivation of protein-tyrosine phosphatases."
  26. Hsu M.F., Lou Y.W., Chen Y.Y. and (Meng T.C.)*  (2010-02)  Handbook of Cell Signaling 2nd Edition by Elsevier  2010, 855-862  "PTP oxidation."
  27. Ku HY, Wu CL, Rabinow L, Chen GC, Meng TC  (2009)  Molecular and Cellular Biology  29(13), 3623-3632  "Organization of F-actin via concerted regulation of Kette by PTP61F and dAbl."
  28. Chien-Cheng Liu, Jan-Hao Li, Cheng-Chung Chang,Yu-Chiang Chao, Hsin-Fei Meng, Sheng-Fu Horng,Cheng-Hsiung Hung and Tzu-Ching Meng  (2009)  JOURNAL OF PHYSICS D-APPLIED PHYSICS  42, 155105 (4 pages)  "Selective real-time nitric oxide detection by functionalized zinc oxide"
  29. Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC  (2008)  J. Biol. Chem.  283(50), 35265-35272  "Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation."
  30. Y. W. Lou, Y. Y. Chen, S. F. Hsu, R. K. Chen, C. L. Lee, K. H. Khoo, N. K. Tonks and T. C. Meng  (2008)  FEBS J  275(1), 69-88  "Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells"
  31. Chang YC, Lin SY, Liang SY, Pan KT, Chou CC, Chen CH, Liao CL, Khoo KH, Meng TC  (2008)  Journal of Proteome Research  7(3), 1055-1066  "Tyrosine phosphoproteomics and identification of substrates of protein tyrosine phosphatase dPTP61F in Drosophila S2 cells by mass spectrometry-based substrate trapping strategy."
  32. M. Halle, Y. C. Liu, S. Hardy, J. F. Theberge, C. Blanchetot, A. Bourdeau, T. C. Meng and M. L. Tremblay  (2007)  Mol Cell Biol  27(3), 1172-1190  "Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response"
  33. Y. Y. Chen, Y. F. Huang, K. H. Khoo and T. C. Meng  (2007)  Methods  42(3), 243-249  "Mass spectrometry-based analyses for identifying and characterizing S-nitrosylation of protein tyrosine phosphatases"
  34. M. Hallé, M. L. Tremblay and T. C. Meng  (2007)  Cell Cycle  6(22), 2773-2781  "Protein Tyrosine Phosphatases: Emerging Regulators of Apoptosis"
  35. Chun-Hung Teng, Wen-Nin Huang and Tzu-Ching Meng  (2007)  J. Biol. Chem  282(39), 28395-28407  "Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress"
  36. C. H. Chen, T. H. Cheng, H. Lin, N. L. Shih, Y. L. Chen, Y. S. Chen, C. F. Cheng, W. S. Lian, T. C. Meng, W. T. Chiu and J. J. Chen  (2006)  Mol Pharmacol  69(4), 1347-1355  "Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2-containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts."
  37. K. K. Nelson, S. Subbaram, K. M. Connor, J. Dasgupta, X. F. Ha, T. C. Meng, N. K. Tonks and J. A. Melendez  (2006)  J Biol Chem  281(20), 14100-14110  "Redox-dependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs"
  38. T. C. Meng, S. F. Hsu and N. K. Tonks  (2005)  Methods  35(1), 28-36  "Development of a modified in-gel assay to identify protein tyrosine phosphatases that are oxidized and inactivated in vivo"
  39. T. C. Meng, D. A. Buckley, S. Galic, T. Tiganis and N. K. Tonks  (2004)  J Biol Chem  279, 37716-37725  "Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B"
  40. T. C. Meng, N. K. Tonks  (2003)  Methods in Enzymology  366, 304-318  "Analysis of the regulation of protein tyrosine phosphatases in vivo by reversible oxidation"
  41. A. Salmeen, J. N. Andersen, M. P. Myers, T. C. Meng, J. A. Hinks, N. K. Tonks and D. Barford  (2003)  Nature  423, 769-773  "Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate"
  42. S. Galic, M. Klingler Hoffmann, M. T. Fodero Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks and T. Tiganis  (2003)  Mol Cell Biol  23, 2096-2108  "Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP"
  43. T. C. Meng, T. Fukada and N. K. Tonks  (2002)  Mol Cell  9, 387-399  "Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo"
  44. M. F. Lin, M. S. Lee, X. W. Zhou, J. C. Andressen, T. C. Meng, S. L. Johansson, W. W. West, R. J. Taylor, J. R. Anderson and F. F. Lin  (2001)  JOURNAL OF UROLOGY  166, 1943-1950  "Decreased expression of cellular prostatic acid phosphatase increases tumorigenicity of human prostate cancer cells"
  45. T. C. Meng, M. S. Lee and M. F. Lin  (2000)  Oncogene  19, 2664-2677  "Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells"
  46. M. F. Lin, T. C. Meng, P. S. Rao, C. Chang, A. H. Schonthal and F. F. Lin  (1998)  J Biol Chem  273, 5939-5947  "Expression of human prostatic acid phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines"
  47. T. C. Meng and M. F. Lin  (1998)  J. Biol. Chem  273, 22096-22104  "Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells"
  48. M. L. Kuo, Y. W. Chou, Y. P. Chau and T. C. Meng  (1996)  Biochem Pharmacol  52, 481-488  "Differential induction of apoptosis in oncogene-transformed NIH 3T3 cells by methylmethanesulfonate"
  49. M. L. Kuo, T. C. Meng and J. K. Lin  (1996)  Carcinogenesis  17, 815-820  "Involvement of glutathione in induction of c-jun proto-oncogene by methylmethanesulfonate in NIH 3T3 cells"
  50. M. F. Lin, T. C. Meng  (1996)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  226, 206-213  "Tyrosine phosphorylation of a 185 kDa phosphoprotein (pp185) inversely correlates with the cellular activity of human prostatic acid phosphatase"

本實驗室的研究工作著重於以下兩個方向:

一. 一氧化氮保護心血管系統免於缺血性病變的傷害: 來自臨床的觀察早已指出,在缺血性心肌梗塞發生時,缺氧及缺氧後重新的血流供應,皆會造成心臟組織嚴重的損壞。最近的研究進一步顯示,具訊息功能的小分子一氧化氮能夠保護心臟組織,避免上述的傷害;因此,若能尋找到提升心臟組織周邊一氧化氮濃度的方法,將對缺血性心肌梗塞的治療上提供具體的幫助。眾多文獻顯示亞硝酸鹽能夠發揮類似一氧化氮的功能,讓心肌組織在缺氧及缺氧後重新的血流供應的情況下維持較好的存活率。根據這樣的觀察,進一步的研究提出許多假設,試圖解釋亞硝酸鹽所扮演的角色。當缺血性心肌梗塞發生時,心臟組織周邊處於低氧的環境,此時局部紅血球中的血紅素有能力將亞硝酸鹽還原為一氧化氮;若一氧化氮能夠穿透紅血球的細胞膜,則此一來自紅血球的一氧化氮就有機會進入周邊的心臟組織,發揮其保護心肌細胞的功能。另一方面,若亞硝酸鹽能直接進入心肌細胞,並透過心肌細胞內生性的酵素將之還原成一氧化氮,亦可發揮其保護功能。本研究的重點,即在於釐清亞硝酸鹽如何透過紅血球中的血紅素,或是心肌細胞內生性的酵素而還原成具有高度活性的一氧化氮,進而保護心臟組織,避免缺血性心肌梗塞造成不可逆的嚴重傷害。我們將採用細胞模式進行機制性的研究,將亞硝酸鹽的還原過程、一氧化氮輸送出紅血球的過程、以及一氧化氮在心肌細胞中促進存活的原因一一釐清。我們並將研究重要訊息分子在這些過程中扮演的角色,以期協助尋找亞硝酸鹽或一氧化氮的標靶。我們預期此一研究成果將對缺血性心肌梗塞的治療策略提供新穎的思考與設計。

二. 蛋白質磷酸化與去磷酸化調控細胞骨架的機制: 過去二十年的研究成果早已指出蛋白質磷酸化的重要性。此種後轉譯修飾作用受到蛋白激酶 kinase及磷酸水解酶 phosphatase之嚴密調控,並扮演極為重要的生理功能。 在本研究中,我們將探討蛋白激酶及磷酸水解酶如何參與細胞骨架蛋白actin重組之過程。我們先前的研究工作已經證實果蠅所表現的骨架蛋白調控分子Kette是一磷酸化的蛋白質,而Kette又可受到磷酸水解酶PTP61F及蛋白激酶dAbl的調控,此時細胞內骨架蛋白Actin的重組則因Kette磷酸化的程度有所快速的變遷,此一重要的發現將作為本計畫的基礎。在後續實驗中,我們將首先釐清Kette、PTP61F及dAbl三者間的關係,並以發育中的果蠅為模式,探討此一調控對Actin參與果蠅器官塑型的重要性。另外,我們將逐一探討其他相關的果蠅骨架蛋白調控分子,包括SCAR/WAVE、Sra-1、Abi,進而瞭解這些分子如何與PTP61F 及dAbl互動,並共同調控果蠅細胞骨架蛋白actin的重組。基於演化上的保守性,類似的機制可能存在於哺乳動物細胞中;因此,我們也將探討蛋白激酶及磷酸水解酶如何透過影響骨架蛋白調控分子的磷酸化程度,進而促成哺乳動物細胞骨架蛋白Actin的快速重組。目前我們將重點放在人類磷酸水解酶PTP1B及蛋白激酶c-Abl針對蛋白調控分子NAP-1的磷酸化所進行的調整。整體而言,此一新穎的研究方向將有助於釐清蛋白質磷酸化及骨架蛋白調控之間的互動關係。

經歷
  • 2014 – 迄今   研究員, 中央研究院生物化學研究所
  • 2017 – 2019   代理副所長, 中央研究院生物化學研究所
  • 2008 – 2014   副研究員, 中央研究院生物化學研究所
  • 2003 – 2008   助研究員, 中央研究院生物化學研究所
  • 1999 – 2003   博士後研究員, 美國紐約州冷泉港實驗室
學歷
  • 1995 – 1999   博士, 生化及分子生物, 美國內布拉斯加州立大學醫學中心
  • 1992 – 1994   碩士, 毒理學, 臺灣大學醫學院
  • 1985 – 1989   學士, 農業化學, 臺灣大學農學院
Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD*, Haj FG*, and Meng TC*
Free Rad Biol Med (2016)
Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC*, Wang AH*
Structure (2015)
Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC* Meng TC*
Mol. Cell. Biol. (2014)
Pan KT, Chen YY, Pu TH, Chao YS, Yang CY, Bomgarden RD, Rogers JC, Meng TC*, Khoo KH*
Antioxidant and Redox Signaling (2014)
Chen KE, Lin SY, Wu MJ, Ho MR, Santhanam A, Chou CC, Meng TC*, Wang AH*
Science Signaling (2014)
Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, Meng TC
Circulation research (2011)
Ku HY, Wu CL, Rabinow L, Chen GC, Meng TC
Molecular and Cellular Biology (2009)
Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC
J. Biol. Chem. (2008)
Chang YC, Lin SY, Liang SY, Pan KT, Chou CC, Chen CH, Liao CL, Khoo KH, Meng TC
Journal of Proteome Research (2008)
M. Halle, Y. C. Liu, S. Hardy, J. F. Theberge, C. Blanchetot, A. Bourdeau, T. C. Meng and M. L. Tremblay
Mol Cell Biol (2007)
  1. Yang CF, Lin TJ, Liu CH, Chen YC, Tang SC, Yang JH, (Meng TC)*, Cheng CF*  (2020-10)  Nutrition  78, 110892  "Eating right for a healthier heart: Food choice contributes to cardiometabolic benefits and reduction of carotid intima-media thickness."
  2. Yang CF, Chen YY, Singh JP, Hsu SF, Liu YW, Yang CY, Chang CW, Chen SN, Shih RH, Hsu SD, Jou YS, Cheng CF, (Meng TC)  (2020-04)  Cardiovascular research  116(5), 1032-1046  "Targeting Protein Tyrosine Phosphatase PTP-PEST for Therapeutic Intervention in Acute Myocardial Infarction."
  3. Chen YJ, Liu YC, Liu YW, Lee YB, Huang HC, Chen YY, Shih YH, Lee YC, Cheng CF, (Meng TC)  (2019-07)  Antioxidants & redox signaling  31(2), 109-126  "Nitrite Protects Neurons Against Hypoxic Damage Through S-nitrosylation of Caspase-6."
  4. Bottini A, Wu DJ, Ai R, Le Roux M, Bartok B, Bombardieri M, Doody KM, Zhang V, Sacchetti C, Zoccheddu M, Lonic A, Li X, Boyle DL, Hammaker D, (Meng TC), Liu L, Corr M, Stanford SM, Lewis M, Wang W, Firestein GS, Khew-Goodall Y, Pitzalis C, Bottini N  (2019-05)  Annals of the rheumatic diseases  78(5), 600-609  "PTPN14 phosphatase and YAP promote TGF beta signalling in rheumatoid synoviocytes."
  5. Hsu SF, Lee YB, Lee YC, Chung AL, Apaya MK, Shyur LF, Cheng CF, Ho FM, (Meng TC)  (2018-05)  The FEBS journal  285(9), 1593-1610  "Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1."
  6. Willoughby LF, Manent J, Allan K, Lee H, Portela M, Wiede F, Warr C, (Meng TC), Tiganis T, Richardson HE  (2017-07)  The FEBS journal  284(14), 2231-2250  "Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants."
  7. Huang YJ, Yang CK, Wei PL, Huynh TT, Whang-Peng J, (Meng TC), Hsiao M, Tzeng YM, Wu AT, Yen Y  (2017-02)  Journal of hematology & oncology  10(1), 60  "Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways."
  8. Huang YJ, Th Wu A, Chiou HY, Chuang MT, (Meng TC), Chien LN, Yen Y  (2017-01)  Oncotarget  8(4), 6642-6651  "Interactive role of diabetes mellitus and female sex in the risk of cholangiocarcinoma: A population-based nested case-control study."
  9. Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD, Haj FG, (Meng TC)  (2016-10)  Free Radical Biology and Medicine  99, 199-213  "S-Nitrosylation of Endogenous Protein Tyrosine Phosphatases in Endothelial Insulin Signaling"
  10. Li MY, Lai PL, Chou YT, Chi AP, Mi YZ, Khoo KH, Chang GD, Wu CW, (Meng TC), Chen GC  (2015-07)  Oncogene  34(29), 3791-3803  "Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation."
  11. Hatzihristidis T, Desai N, Hutchins AP, (Meng TC), Tremblay ML, Miranda-Saavedra D  (2015-04)  FEBS letters  589(9), 951-966  "A Drosophila-centric view of protein tyrosine phosphatases."
  12. Chen KE, Li MY, Chou CC, Ho MR, Chen GC, (Meng TC), Wang AH  (2015-04)  Structure  23(4), 653-664  "Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases."
  13. Tchankouo-Nguetcheu S, Udinotti M, Durand M, (Meng TC), Taouis M, Rabinow L  (2014-10)  Molecular genetics and genomics  289(5), 795-806  "Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B."
  14. Kai-En Chen, Shu-Yu Lin, Mei-Ju Wu, Meng-Ru Ho, Abirami Santhanam, Chia-Cheng Chou, (Tzu-Ching Meng), and Andrew H. -J. Wang  (2014-10)  Science Signaling  7(347), ra98  "Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain–modulated complex formation"
  15. Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC, (Meng TC)  (2014-05)  Molecular and cellular biology  34(9), 1594-1606  "Ecdysone-induced receptor tyrosine phosphatase PTP52F regulates Drosophila midgut histolysis by enhancement of autophagy and apoptosis."
  16. Pan KT, Chen YY, Pu TH, Chao YS, Yang CY, Bomgarden RD, Rogers JC, (Meng TC), Khoo KH  (2014-03)  ANTIOXIDANTS & REDOX SIGNALING  20(9), 1365-1381  "Mass Spectrometry-Based Quantitative Proteomics for Dissecting Multiplexed Redox Cysteine Modifications in Nitric Oxide-Protected Cardiomyocyte Under Hypoxia."
  17. Chang YC, Tang HW, Liang SY, Pu TH, (Meng TC), Khoo KH, Chen GC  (2013-05)  Journal of proteome research  12(5), 2138-2150  "Evaluation of Drosophila metabolic labeling strategies for in vivo quantitative proteomic analyses with applications to early pupa formation and amino acid starvation."
  18. Buszard BJ, Johnson TK, (Meng TC), Burke R, Warr CG, Tiganis T  (2013-04)  Molecular and cellular biology  33(7), 1345-1356  "The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine phosphatase 61F regulate Drosophila growth, life span, and fecundity."
  19. Santhanam A, Liang SY, Chen DY, Chen GC*, (Meng TC)*  (2013-01)  The FEBS journal  280(2), 476-488  "Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition."
  20. Chen DY, Li MY, Wu SY, Lin YL, Tsai SP, Lai PL, Lin YT, Kuo JC, (Meng TC), Chen GC  (2012)  Journal of cell science  125(20), 4841-4852.  "The Bro1 domain-containing Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration."
  21. Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, (Meng TC)  (2011-12)  Circulation research  109,1375-1386  "Nitrite-Mediated S-Nitrosylation of Caspase-3 Prevents Hypoxia-Induced Endothelial Barrier Dysfunction."
  22. Wu CL, Buszard B, Teng CH, Chen WL, Warr C, Tiganis T, (Meng TC)  (2011-10)  Biochemical journal  439(1), 151-159  "Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signaling."
  23. Yu-Chiang Chao, Shih-De Yeh, Hsiao-Wen Zan, Gao-Fong Chang, Hsin-Fei Meng, Chen-Hsiung Hung, (Tzu-Ching Meng)  (2011-05)  ORGANIC ELECTRONICS  12(5), 751-755  "Integrated semiconductor optoelectronic devices for real-time and indicator-free detection of aqueous nitric oxide."
  24. Chao Y.C., Yeh S.D., Zan H.W., Hong Y.R., Wu M.C., Chang G.F., Tsai P.Y., Meng H.F., Hung C.H., (Meng T.C.), Hsu C.S., and Horng S.F.  (2010-06)  APPLIED PHYSICS LETTERS  96, 223702(1-3)  "Real-time and indicator-free detection of aqueous nitric oxide with hydrogel film."
  25. Hsu MF, (Meng TC)  (2010-03)  JOURNAL OF BIOLOGICAL CHEMISTRY  285(11), 7919-7928  "Enhancement of insulin responsiveness by nitric oxide-mediated inactivation of protein-tyrosine phosphatases."
  26. Hsu M.F., Lou Y.W., Chen Y.Y. and (Meng T.C.)*  (2010-02)  Handbook of Cell Signaling 2nd Edition by Elsevier  2010, 855-862  "PTP oxidation."
  27. Ku HY, Wu CL, Rabinow L, Chen GC, Meng TC  (2009)  Molecular and Cellular Biology  29(13), 3623-3632  "Organization of F-actin via concerted regulation of Kette by PTP61F and dAbl."
  28. Chien-Cheng Liu, Jan-Hao Li, Cheng-Chung Chang,Yu-Chiang Chao, Hsin-Fei Meng, Sheng-Fu Horng,Cheng-Hsiung Hung and Tzu-Ching Meng  (2009)  JOURNAL OF PHYSICS D-APPLIED PHYSICS  42, 155105 (4 pages)  "Selective real-time nitric oxide detection by functionalized zinc oxide"
  29. Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC  (2008)  J. Biol. Chem.  283(50), 35265-35272  "Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation."
  30. Y. W. Lou, Y. Y. Chen, S. F. Hsu, R. K. Chen, C. L. Lee, K. H. Khoo, N. K. Tonks and T. C. Meng  (2008)  FEBS J  275(1), 69-88  "Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells"
  31. Chang YC, Lin SY, Liang SY, Pan KT, Chou CC, Chen CH, Liao CL, Khoo KH, Meng TC  (2008)  Journal of Proteome Research  7(3), 1055-1066  "Tyrosine phosphoproteomics and identification of substrates of protein tyrosine phosphatase dPTP61F in Drosophila S2 cells by mass spectrometry-based substrate trapping strategy."
  32. M. Halle, Y. C. Liu, S. Hardy, J. F. Theberge, C. Blanchetot, A. Bourdeau, T. C. Meng and M. L. Tremblay  (2007)  Mol Cell Biol  27(3), 1172-1190  "Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response"
  33. Y. Y. Chen, Y. F. Huang, K. H. Khoo and T. C. Meng  (2007)  Methods  42(3), 243-249  "Mass spectrometry-based analyses for identifying and characterizing S-nitrosylation of protein tyrosine phosphatases"
  34. M. Hallé, M. L. Tremblay and T. C. Meng  (2007)  Cell Cycle  6(22), 2773-2781  "Protein Tyrosine Phosphatases: Emerging Regulators of Apoptosis"
  35. Chun-Hung Teng, Wen-Nin Huang and Tzu-Ching Meng  (2007)  J. Biol. Chem  282(39), 28395-28407  "Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress"
  36. C. H. Chen, T. H. Cheng, H. Lin, N. L. Shih, Y. L. Chen, Y. S. Chen, C. F. Cheng, W. S. Lian, T. C. Meng, W. T. Chiu and J. J. Chen  (2006)  Mol Pharmacol  69(4), 1347-1355  "Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2-containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts."
  37. K. K. Nelson, S. Subbaram, K. M. Connor, J. Dasgupta, X. F. Ha, T. C. Meng, N. K. Tonks and J. A. Melendez  (2006)  J Biol Chem  281(20), 14100-14110  "Redox-dependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs"
  38. T. C. Meng, S. F. Hsu and N. K. Tonks  (2005)  Methods  35(1), 28-36  "Development of a modified in-gel assay to identify protein tyrosine phosphatases that are oxidized and inactivated in vivo"
  39. T. C. Meng, D. A. Buckley, S. Galic, T. Tiganis and N. K. Tonks  (2004)  J Biol Chem  279, 37716-37725  "Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B"
  40. T. C. Meng, N. K. Tonks  (2003)  Methods in Enzymology  366, 304-318  "Analysis of the regulation of protein tyrosine phosphatases in vivo by reversible oxidation"
  41. A. Salmeen, J. N. Andersen, M. P. Myers, T. C. Meng, J. A. Hinks, N. K. Tonks and D. Barford  (2003)  Nature  423, 769-773  "Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate"
  42. S. Galic, M. Klingler Hoffmann, M. T. Fodero Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks and T. Tiganis  (2003)  Mol Cell Biol  23, 2096-2108  "Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP"
  43. T. C. Meng, T. Fukada and N. K. Tonks  (2002)  Mol Cell  9, 387-399  "Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo"
  44. M. F. Lin, M. S. Lee, X. W. Zhou, J. C. Andressen, T. C. Meng, S. L. Johansson, W. W. West, R. J. Taylor, J. R. Anderson and F. F. Lin  (2001)  JOURNAL OF UROLOGY  166, 1943-1950  "Decreased expression of cellular prostatic acid phosphatase increases tumorigenicity of human prostate cancer cells"
  45. T. C. Meng, M. S. Lee and M. F. Lin  (2000)  Oncogene  19, 2664-2677  "Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells"
  46. M. F. Lin, T. C. Meng, P. S. Rao, C. Chang, A. H. Schonthal and F. F. Lin  (1998)  J Biol Chem  273, 5939-5947  "Expression of human prostatic acid phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines"
  47. T. C. Meng and M. F. Lin  (1998)  J. Biol. Chem  273, 22096-22104  "Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells"
  48. M. L. Kuo, Y. W. Chou, Y. P. Chau and T. C. Meng  (1996)  Biochem Pharmacol  52, 481-488  "Differential induction of apoptosis in oncogene-transformed NIH 3T3 cells by methylmethanesulfonate"
  49. M. L. Kuo, T. C. Meng and J. K. Lin  (1996)  Carcinogenesis  17, 815-820  "Involvement of glutathione in induction of c-jun proto-oncogene by methylmethanesulfonate in NIH 3T3 cells"
  50. M. F. Lin, T. C. Meng  (1996)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  226, 206-213  "Tyrosine phosphorylation of a 185 kDa phosphoprotein (pp185) inversely correlates with the cellular activity of human prostatic acid phosphatase"