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。
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)