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Dr. Tzu-Ching  Meng
Research Fellow & Acting Associate Director
Room 601, Institute of Biological Chemistry, Academia Sinica
128, Academia Road Sec. 2, Nankang, Taipei 115, Taiwan
TEL: +886-2-2785-5696 ext. 6010
FAX: +886-2-2788-9759
tcmeng@gate.sinica.edu.tw
Tzu-Ching  Meng's Website


Two main focuses of research work are being carried out in the laboratory at this time: (1) The role of nitric oxide (NO) in protection of cardiovascular system under ischemia stress It has been well documented that cardiac tissues undergo severe injury when ischemia or ischemia-reperfusion (I/R) occurs, leading to irreversible heart failure and loss of life in many cases. Interestingly, this deteriorated process is prevented by the action of small signaling molecule nitric oxide (NO). Therefore, identification of therapeutic interventions that enhance the cardiac NO level for protecting tissues is desperately essential. Recent studies suggested that nitrite, which is chemically stable and functions as a natural reservoir of NO in blood and tissue, may play an important role in protecting heart against ischemia- or I/R-induced damage. Investigations further demonstrated that the deoxygenated form of hemoglobin in red blood cells (RBCs) may function as a nitrite reductase, thus generating bioactive form of NO, which, if exported out from RBCs, exerts as a signaling molecule to prevent cell injury of nearby cardiomyocytes under I/R conditions. Moreover, it was also proposed that endogenous nitrite reductase expressed in cardiomyocytes may convert nitrite to bioactive NO under ischemia, thus preventing heart tissues from subsequent reperfusion-induced damage. With these critical observations as background, it is entirely appropriate to formulate a proposal in which the mechanistic details of nitrite-mediated protective effect on ischemic heart are thoroughly investigated. In the current study, we will used cell based models under hypoxia and hypoxia-reoxygenation to delineate the underlying mechanisms through which specific signaling pathways act to facilitate reduction of nitrite to NO in both RBCs and cardiomyocytes, to export the bioactive form of NO out of RBCs, and to promote the survival of cardiomyocytes in coordination with NO. Important signaling modulators susceptible to NO-induced regulation of enzymatic activity, such as caspases and protein tyrosine phosphatases, will be our primary focuses to investigate the beneficial effect of NO and nitrite on myocardial survival. This information will certainly advance our understanding in nitrite-mediated prevention of heart failure under pathological processes, such as I/R. In addition, some hopeful clues for designing therapeutic strategies that may rescue ischemic heart would be provided. (2) The role of protein kinases and phosphatases in regulation of actin dynamics A substantial body of evidence clearly demonstrates that reversible tyrosine phosphorylation plays a critical role in regulating a diverse range of biological processes such as development, proliferation, differentiation, migration and death in metazoans. In order to maintain the dynamic nature of tyrosine phosphorylation for controlling proper cellular functions, the action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) must be tightly coordinated. In the present study, we focus on investigation of the role of PTPs and PTKs for their potential in the control of actin organization. Our preliminary data clearly show a novel connection between reversible tyrosine phosphorylation signaling and regulation of actin reorganization in Drosophila. Specifically, our findings demonstrate for the first time that Kette, a key component in SCAR/WAVE complex, is a tyrosine phosphorylated (p-Tyr) protein. The p-Tyr level of Kette is coordinately regulated by Drosophila tyrosine phosphatase PTP61F and the kinase dAbl. Importantly, the phosphorylation-dependent network controlled by PTP61F and dAbl plays a pivotal role in Kette-mediated actin organization and lamella formation in Drosophila cells. As these observations as background, we will employ several approaches at the biochemical, genetic and cellular levels to reveal the critical role of Kette, PTP61F and dAbl in signal transduction for controlling actin dynamics and the subsequent effect on developmental process. We will investigate the underlying mechanism that determines PTP61F or dAbl-mediated Kette activity for regulation of F-actin assembly. The biological significance of such phosphorylation-dependent regulation will be tested by genetic interactions during Drosophila development. We will also test whether PTP61F regulates actin organization through the coordinated control of other components of SCAR/WAVE complex, including SCAR/WAVE itself, Sra-1 and Abi, which have been identified as potential substrates of PTP61F in our recent study. The functional role of dAbl to promote F-actin assembly through tyrosine phosphorylation of those components in SCAR/WAVE complex will be further examined. We will further test the possibility that reversible phosphorylation-dependent regulation of actin cytoskeleton is an evolutionarily conserved event across species. For this purpose, in addition to the studies using Drosophila as a model, we will test our hypothesis by examining the role of PTPs and PTKs that participate in regulation of SCAR/WAVE complex in mammalian cells. Our primary focus is on the actin organization controlled by the interaction between PTP1B and NAP-1, which represent the mammalian ortholog of PTP61F and Kette, respectively. The potential of c-Abl, a mammalian ortholog of dAbl, in regulating actin organization through tyrosine phosphorylation of NAP-1 will be examined. Through the comprehensive investigation proposed in this application, our findings will shed new light on the coordinated action among critical signaling molecules for controlling actin dynamics.

1995,08 - 1999,07 Ph.D., Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
1992,08 - 1994,06 M.S., Toxicology, National Taiwan University College of Medicine
1985,08 - 1989,06 B.S., Agricultural Chemistry, National Taiwan University College of Agriculture

2017,08 - present Acting Associate Director, Institute of Biological Chemistry, Academia Sinica
2014,03 - present Research Fellow, Institute of Biological Chemistry, Academia Sinica
2008 - 2014,03 Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica
2003 - 2008 Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
1999,08 - 2003,05 Post-doctoral Research Fellow, Cold Spring Harbor Laboratory, NY, USA

    Publications List
Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signaling.
Wu CL, Buszard B, Teng CH, Chen WL, Warr C, Tiganis T, Meng TC Biochemical journal (2011)
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)
Enhancement of insulin responsiveness by nitric oxide-mediated inactivation of protein-tyrosine phosphatases.
Hsu MF, Meng TC JOURNAL OF BIOLOGICAL CHEMISTRY (2010)
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)
Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress.
Chun-Hung Teng, Wen-Nin Huang and Tzu-Ching Meng J. Biol. Chem (2007)
Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B.
T. C. Meng, D. A. Buckley, S. Galic, T. Tiganis and N. K. Tonks J Biol Chem (2004)
Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo.
T. C. Meng, T. Fukada and N. K. Tonks Mol Cell (2002)

Updated 2017.03.08

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