中央研究院 生物化學研究所

研究領域與專長

研究主題一
以腸道微菌代謝物開拓大腸直腸癌精準輔助治療

腸道微生態失調與人類疾病的發展息息相關。大腸癌患者之腸道微菌叢明顯與健康族群不同，而此失調現象在治療後仍然持續。腸道微菌叢持續不良可能影響癌症病患的預後，但目前仍無有效方法來解決這個問題。我們認為腸道菌代謝物應能直接作用於宿主細胞受體上，藉由調節細胞訊息，改善大腸癌患者因腸道微生態失調所造成之負面影響，並增進病患存活率與生活品質。以微菌代謝物來調節宿主細胞受體作為大腸癌輔助療法，是一個突破性的概念及嶄新的藥物開發課題。我們招募大腸癌病患，藉由臨床大數據分析找出重要代謝物與受體，再以細胞與動物模式確認其功能。而代謝物與受體之間的互動關係，則以我們擅長的結構生物學方法來釐清。此研究的目標為開發第一個微菌代謝體藥物，經過精準評估後，施予適合的大腸癌患者來發揮有效之輔助治療。

研究主題二
藉由腸道微菌代謝物調節心臟功能以促進健康老化

在高度分化的心肌細胞中若有氧化失活態蛋白的沈積，會導致心肌細胞蛋白的平衡失調，此為心臟老化的一個顯著特徵。此現象進一步造成老化心臟對於壓力的極度敏感，使個體的心血管疾病風險顯著上升。於是，使心臟可以在老化過程中維持健康的一個重要挑戰，便是促使氧化態且失去活性的心肌蛋白被正常代謝。為此，我們尋找有效的腸道菌代謝物來調控心肌細胞的氧化壓力與蛋白裂解平衡。我們的研究目標為釐清腸道菌代謝物調控心肌細胞蛋白平衡的效用與機制。當目標代謝物的功能被證實後，我們將運用此代謝物與其衍生物，協助個體在老化的過程中仍能保持心臟健康。

學經歷

• 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

• 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

主要著作

S-Nitrosylation of endogenous protein tyrosine phosphatases in endothelial insulin signaling. 
Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD*, Haj FG*, and Meng TC* 
Free Rad Biol Med (2016)

Substrate specificity and plasticity of FERM-containing protein tyrosine phosphatases. 
Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC*, Wang AH* 
Structure (2015)

Ecdysone-induced receptor tyrosine phosphatase PTP52F regulates Drosophila midgut histolysis by enhancement of autophagy and apoptosis. 
Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC* Meng TC* 
Mol. Cell. Biol. (2014)

Mass spectrometry based quantitative proteomics for dissecting multiplexed redox cysteine modifications in nitric oxide-protected cardiomyocyte under hypoxia. 
Pan KT, Chen YY, Pu TH, Chao YS, Yang CY, Bomgarden RD, Rogers JC, Meng TC*, Khoo KH* 
Antioxidant and Redox Signaling (2014)

Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain modulated complex formation. 
Chen KE, Lin SY, Wu MJ, Ho MR, Santhanam A, Chou CC, Meng TC*, Wang AH* 
Science Signaling (2014)

Nitrite-Mediated S-Nitrosylation of Caspase-3 Prevents Hypoxia-Induced Endothelial Barrier Dysfunction. 
Lai YC, Pan KT, Chang GF, Hsu CH, Khoo KH, Hung CH, Jiang YJ, Ho FM, Meng TC 
Circulation research (2011)

Organization of F-actin via concerted regulation of Kette by PTP61F and dAbl. 
Ku HY, Wu CL, Rabinow L, Chen GC, Meng TC 
Molecular and Cellular Biology (2009)

Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation. 
Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC 
J. Biol. Chem. (2008)

Tyrosine phosphoproteomics and identification of substrates of protein tyrosine phosphatase dPTP61F in Drosophila S2 cells by mass spectrometry-based substrate trapping strategy. 
Chang YC, Lin SY, Liang SY, Pan KT, Chou CC, Chen CH, Liao CL, Khoo KH, Meng TC 
Journal of Proteome Research (2008)

Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response. 
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. Singh JP, Chen YY, Huang YT, Hsu STD, (Meng TC)*  (2023-03)  Methods in enzymology  682, 351-374  "Application of hybrid biophysical-biochemical methods to unravel the molecular basis for auto-inhibition and activation of protein tyrosine phosphatase TCPTP/PTPN2."
   
2. Yang CY, Yang CF, Tang XF, Machado LESF, Singh JP, Peti W, Chen CS, (Meng TC)*  (2023-01)  Free radical biology & medicine  194, 147-159  "Active-site cysteine 215 sulfonation targets protein tyrosine phosphatase PTP1B for Cullin1 E3 ligase-mediated degradation."
   
3. Singh JP, Li Y, Chen YY, Hsu STD, Page R, Peti W*, (Meng TC)*  (2022-01)  Nature Communications  13(1), 94  "The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1."
   
4. Singh JP, Lin MJ, Hsu SF, Peti W, Lee CC*, (Meng TC)*  (2021-12)  Biochemistry  60(51), 3856-3867  "Crystal Structure of TCPTP Unravels an Allosteric Regulatory Role of Helix alpha7 in Phosphatase Activity."
   
5. 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."
   
6. 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."
   
7. 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."
   
8. 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."
   
9. 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."
   
10. 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."
    
11. 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."
    
12. 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."
    
13. 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"
    
14. 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."
    
15. 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."
    
16. 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."
    
17. 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."
    
18. 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"
    
19. 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."
    
20. 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."
    
21. 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."
    
22. 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."
    
23. 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."
    
24. 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."
    
25. 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."
    
26. 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."
    
27. 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."
    
28. 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."
    
29. 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."
    
30. 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."
    
31. 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."
    
32. 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"
    
33. 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."
    
34. 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"
    
35. 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."
    
36. 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"
    
37. 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"
    
38. M. Hallé, M. L. Tremblay and T. C. Meng  (2007)  Cell Cycle  6(22), 2773-2781  "Protein Tyrosine Phosphatases: Emerging Regulators of Apoptosis"
    
39. 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"
    
40. 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."
    
41. 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"
    
42. 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"
    
43. 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"
    
44. 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"
    
45. 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"
    
46. 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"
    
47. 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"
    
48. 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"
    
49. 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"
    
50. 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"
    
51. 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"
    
52. 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"
    
53. 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"
    
54. 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"