Division of Life Science
 
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Karl Wah-Keung TSIM

PhD University of Cambridge
Chair Professor

Email: botsim@ust.hk

Laboratory Homepage

Research Interests
Prof Tsim has chosen the vertebrate neuromuscular junctions as the model system to study the cellular and molecular events that lead to the formation of synapses during development and regeneration. The post-synaptic specializations, induced by motor neuron, include the expression and aggregation of acetylcholine receptors (AChRs), acetylcholinesterase (AChE) and other synaptic molecules in the muscle cell. Results from our laboratory have indicated that adenosine 5'-triphosphate (ATP), co-released with acetylcholine from the motor neurons, induces the expression of AChR/AChE by activating its receptors, P2Y subtype. Prof Tsim intends to use molecular genetic methods to : (i) determine the role of ATP and P2Y receptors in directing the formation of post-synaptic specializations; (ii) reveal the signaling pathway of P2Y receptor-mediated AChR/AChE gene activation in muscle; (iii) map the transcriptional elements of the catalytic subunit and the collagen-tail (ColQ) subunit of AChE during muscle development. In addition, Prof Tsim has developed molecular technique to determine the genetic and chemical properties of traditional Chinese medicine (TCM).

Representative Publications

Biochemistry and neurobiology (from 2005):

1.       Li, W., Pi, R., Chan, H.H., Fu, H., Lee, N.T., Tsang, H.W., Pu, Y., Chang, D.C., Li, C., Luo, J., Xiong, K., Li, Z., Xue, H., Carlier, P.R., Pang, Y., Tsim, K.W.K., Li, M. and Han, Y. (2005): Novel dimeric acetylcholinesterase inhibitor bis7-tacrine, but not donepezil, prevents glutamate-induced neuronal apoptosis by blocking N-methyl-D-aspartate receptors. J Biol Chem. 280: 18179-18188.

2.       Ling, K.K., Siow, N.L., Choi, R.C. and Tsim, K.W.K. (2005): ATP potentiates the formation of AChR aggregate in the co-culture of NG108-15 cells with C2C12 myotubes. FEBS Lett. 579: 2469-2474.

3.       Ting, A.K., Siow, N.L., Kong, L.W. and Tsim, K.W.K. (2005): Transcriptional regulation of acetylcholinesterase-associated collagen ColQ in fast- and slow-twitch muscle fibers. Chem Biol Interact. 157-158: 63-70.

4.       Siow, N.L., Xie, H.Q., Choi, R.C. and Tsim, K.W.K. (2005): ATP induces the post-synaptic gene expression in neuron-neuron synapses: Transcriptional regulation of AChE catalytic subunit. Chem Biol Interact. 157-158: 423-6.

5.       Xie, H.Q., Siow, N.L., Peng, H.B., Massouli, J. and Tsim, K.W.K. (2005): Regulation of PRiMA: membrane anchor of acetylcholinesterase (AChE) in neuron and muscle. Chem Biol Interact. 157-158: 432.

6.       Li, W., Lee, N.T., Fu, H., Kan, K.K., Pang, Y., Li, M., Tsim, K.W.K., Li, X. and Han, Y. (2006): Neuroprotection via inhibition of nitric oxide synthase by bis(7)-tacrine. Neuroreport. 17: 471-474.

7.       Ji, Z.N., Dong, T.T., Ye, W.C., Choi, R.C., Lo, C.K. and Tsim, K.W.K. (2006): Ginsenoside Re attenuate beta-amyloid and serum-free induced neurotoxicity in PC12 cells. J Ethnopharmacol. 107: 48-52.

8.       Fu, H., Li, W., Lao, Y., Luo, J., Lee, N.T., Kan, K.K., Tsang, H.W., Tsim K.W.K., Pang, Y., Li, Z., Chang, D.C., Li, M. and Han, Y. (2006): Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels. J Neurochem. 98: 1400-1410.

9.       Wan, D.C., Zhang, X., Siow, N.L., Xie, H.Q. and Tsim, K.W.K. (2006): Chick acetylcholinesterase promoter regulation. J Mol Neurosci. 30: 33-34.

10.     Tsim, K.W.K., Xie, H.Q., Ting, A.K., Siow, N.L., Ling, K.K. and Kong, L.W. (2006): Transcriptional control of different acetylcholinesterase subunits in formation and maintenance of vertebrate neuromuscular junctions. J Mol Neurosci. 30: 189-192.

11.     Zhu, H., Gao, W., Jiang, H., Jin, Q.H., Shi, Y.F., Tsim, K.W.K. and Zhang, X.J. (2007): Regulation of acetylcholinesterase expression by calcium signaling during calcium ionophore A23187- and thapsigargin-induced apoptosis. Int J Biochem Cell Biol. 39: 93-108.

12.     Li, W., Xue, J., Niu, C., Fu, H., Lam, C.S., Luo, J., Chan, H.H., Xue, H., Kan, K.K., Lee, N.T., Li, C., Pang, Y., Li, M., Tsim, K.W.K., Jiang, H., Chen, K., Li, X. and Han, Y. (2007): Synergistic neuroprotection by bis(7)-tacrine via concurrent blockade of N-methyl-D-aspartate receptors and neuronal nitric-oxide synthase. Mol Pharmacol. 71: 1258-1267.

13.     Zhu, J.T., Choi, R.C., Chu, G.K., Cheung, A.W., Gao, Q.T., Li, J., Jiang, Z.Y., Dong, T.T. and Tsim, K.W.K. (2007): Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J Agric Food Chem. 55: 2438-2445.

14.     Xie, H.Q., Choi, R.C., Leung, K.W., Siow, N.L., Kong, L.W., Lau, F.T., Peng, H.B. and Tsim, K.W.K. (2007): Regulation of a transcript encoding the proline-rich membrane anchor of globular muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating nerves. J Biol Chem. 282: 11765-11775.

15.     Choi, R.C., Ting, A.K., Lau, F.T., Xie, H.Q., Leung, K.W., Chen, V.P., Siow, N.L and Tsim, K.W.K. (2007): Calcitonin gene-related peptide induces the expression of acetylcholinesterase-associated collagen ColQ in muscle: a distinction in driving two different promoters between fast- and slow-twitch muscle fibers. J Neurochem. 102: 1316-1328.

16.     Fu, H., Li, W., Liu, Y., Lao, Y., Liu, W., Chen, C., Yu, H., Lee, N.T., Chang, D.C., Li, P., Pang, Y., Tsim, K.W.K., Li, M. and Han, Y. (2007): Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons. J Proteome Res. 6: 2435-2446.

17.     Fu, H., Li, W., Luo, J., Lee, N.T., Li, M., Tsim, K.W.K., Pang, Y., Youdim, M.B. and Han, Y. (2008): Promising anti-Alzheimer's dimer bis(7)-tacrine reduces beta-amyloid generation by directly inhibiting BACE-1 activity. Biochem Biophys Res Commun. 366: 631-636.

18.     Choi, R.C., Simon, J., Tsim, K.W.K. and Barnard, E.A. (2008): Constitutive and agonist-induced dimerizations of the P2Y1 receptor: relationship to internalization and scaffolding. J Biol Chem. 283: 11050-11063.

19.     Tsim, K.W.K., Choi, R.C., Xie, H.Q., Zhu, J.T., Leung, K.W., Lau, F.T., Chu, G.K., Chen, V.P., Mok, M.K., Cheung, A.W. and Bi, C.W. (2008). Transcriptional control of different subunits of AChE in muscles: signals triggered by the motor nerve-derived factors. Chem Biol Interact. 175: 58-63.

20.     Choi, R.C., Mok, M.K., Cheung, A.W., Siow, N.L., Xie, H.Q. and Tsim, K.W.K. (2008). Regulation of PRiMA-linked G(4) AChE by a cAMP-dependent signaling pathway in cultured rat pheochromocyoma PC12 cells. Chem Biol Interact. 175: 76-78.

21.     Xie, H.Q., Leung, K.W., Chen, V.P., Lau, F.T., Liu, L.S., Choi, R.C. and Tsim, K.W.K. (2008). The promoter activity of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase in muscle: suppressive roles of myogenesis and innervating nerve. Chem Biol Interact. 175: 79-82.

22.     Lau, F.T., Choi, R.C., Xie, H.Q., Leung, K.W., Chen, V.P., Zhu, J.T., Bi, C.W., Chu, G.K. and Tsim, K.W.K. (2008). Myocyte enhancer factor 2 mediates acetylcholine-induced expression of acetylcholinesterase- associated collagen ColQ in cultured myotubes. Mol Cell Neurosci. 39: 429-438.

23.     Ng, Y.P., Wu, Z., Wise, H., Tsim, K.W.K., Wong, Y.H. and Ip, N.Y. (2009). Differential and Synergistic effect of nerve growth factor and cAMP on the regulation of early response genes during neuronal differentiation. Neurosignals. 17: 111-120.

24.     Xie, H.Q., Choi, R.C., Leung, K.W., Chen, V.P., Chu, G.K. and Tsim, K.W.K. (2009) Transcriptional regulation of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase in neuron: an inductive effect of neuron differentiation. Brain Res. (Published online)

 

Traditional Chinese medicine (from 2005):

1.       Tsim, K.W.K. (2005): Danggui Buxue Tang (DBT, Chinese Angelica Decoction): a sample trial in TCM standardization. Asia-Pacific Biotech News (APBN). 8: 1316-1321.

2.       Zhao, K.J., Dong, T.T.X., Lo, CK., Tu, P.F. and Tsim, K.W.K. (2005): Species identification of Dyers woad leaf by DNA sequences of 5S-rRNA spacer domain and random amplified polymorphic DNA (RAPD). Oriental Pharmacy and Experimental Medicine. 5: 117-123.

3.       Cheung, J.K.H., Li, S.P. and Tsim, K.W.K. (2005): Authentication and quality control of Cordyceps sinensis, a traditional Chinese medicine known as winter-worm summer-grass. Oriental Pharmacy and Experimental Medicine. 5: 262-271.

4.       Yang, F.Q., Li, S.P., Chen, Y., Lao, S.C., Wang, Y.T., Dong, T.T.X. and Tsim, K.W.K. (2005): Identification and quantitation of eleven sesquiterpenes in three species of Curcuma rhizomes by pressurized liquid extraction and gas chromatography-mass spectrometry. J Pharm Biomed Anal. 39: 552-558.

5.       Carles, M., Cheung, M.K., Moganti, S., Dong, T.T.X., Tsim, K.W.K., Ip, N.Y. and Sucher, N.J. (2005): A DNA microarray for the authentication of toxic traditional Chinese medicinal plants. Planta Med. 71: 580-584.

6.       Xia, Q., Zhao, K.J., Huang, Z.G., Zhang, P., Dong, T.T.X., Li, S.P. and Tsim, K.W.K. (2005): Molecular genetic and chemical assessment of Rhizoma Curcumae in China. J Agric Food Chem. 53: 6019-6026.

7.       Dong, T.T.X., Zhao, K.J., Huang, W.Z., Leung, K.W. and Tsim, K.W.K. (2005): Orthogonal array design in optimizing the extraction efficiency of active constituents from roots of Panax notoginseng. Phytother Res. 19: 684-688.

8.       Wu, X.M., Gao, X.M., Tsim, K.W.K. and Tu, P.F. (2005): An arabinogalactan isolated from the stems of Cistanche deserticola induces the proliferation of cultured lymphocytes. Int J Biol Macromol. 37: 278-282.

9.       Kung, S.D. and Tsim, K.W.K. (2006): Modernization of Traditional Chinese Medicine-A Prospect From Western Medicine (從西方思維看中藥現代化). Joint Publishing (HK) Co. Ltd.

10.     Li, S.P., Yang, F.Q. and Tsim, K.W.K. (2006): Quality control of Cordyceps sinensis, a valued traditional Chinese medicine. J Pharm Biomed Anal. 41: 1571-1584.

11.     Dong, T.T.X., Zhao, K.J., Gao, Q.T., Ji, Z.N., Zhu, T.T., Li, J., Duan, R., Cheung, A.W. and Tsim, K.W.K. (2006): Chemical and biological assessment of a chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties. J Agric Food Chem. 54: 2767-2774.

12.     Mak, D.H., Chiu, P.Y., Dong, T.T.X., Tsim, K.W.K. and Ko, K.M. (2006): Dang-Gui Buxue Tang produces a more potent cardioprotective effect than its component herb extracts and enhances glutathione status in rat heart mitochondria and erythrocytes. Phytother Res. 20: 561-567.

13.     Li, S.P., Zhang, G.H., Zeng, Q., Huang, Z.G., Wang, Y.T., Dong, T.T.X. and Tsim, K.W.K. (2006): Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine. 13: 428-433.

14.     Gao, Q.T., Cheung, J.K., Li, J., Chu, G.K., Duan, R., Cheung, A.W., Zhao, K.J., Dong, T.T.X. and Tsim, K.W.K. (2006): A Chinese herbal decoction, Danggui Buxue Tang, prepared from Radix Astragali and Radix Angelicae Sinensis stimulates the immune responses. Planta Med. 72: 1227-31.

15.     Wu, X., Dai, H., Huang, L., Gao, X., Tsim, K.W.K., and Tu, P. (2006): A fructan, from Radix ophiopogonis, stimulates the proliferation of cultured lymphocytes: structural and functional analyses. J Nat Prod. 69: 1257-1260.

16.     Ji, Z.N., Zhao, W.Y., Liao, G.R., Choi, R.C., Lo, C.K., Dong, T.T.X. and Tsim, K.W.K. (2006): In vitro estrogenic activity of formononetin by two bioassay systems. Gynecol Endocrinol. 22: 578-584.

17.     Wan, J.B., Li, P., Li, S., Wang, Y., Dong, T.T.X. and Tsim, K.W.K. (2007): Simultaneous determination of 11 saponins in Panax notoginseng using HPLC-ELSD and pressurized liquid extraction. J Sep Sci. 29: 2190-2196.

18.     Gao, Q.T., Choi, R.C., Cheung, A.W., Zhu, J.T., Li, J., Chu, G.K., Duan, R., Cheung, J.K., Jiang, Z.Y., Dong, X.B., Zhao, K.J., Dong, T.T.X. and Tsim, K.W.K. (2007): Danggui buxue tang – a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells. FEBS Lett. 581: 233-240.

19.     Chiu, P.Y., Leung, H.Y., Siu, A.H., Poon, M.K., Dong, T.T.X., Tsim, K.W.K. and Ko, K.M. (2007): Dang-Gui Buxue Tang protects against oxidant injury by enhancing cellular glutathione in H9c2 cells: role of glutathione synthesis and regeneration. Planta Med. 73: 134-141.

20.     Li, J., Dong, X., Jiang, Y., Gao, Q., Jiang, Z., Cheung, A.W., Duan, R., Dong, T.T.X., Tu, P. and Tsim, K.W.K. (2007): Simultaneous determination of phenols in Radix Polygalae by high performance liquid chromatography: quality assurance of herbs from different regions and seasons. J Sep Sci. 30: 2583-2589.

21.     Ng, K.L., Lam, C.C., Fu, Z., Han, Y.F., Tsim, K.W.K. and Wong, W.K. (2007): Cloning and characterization of the yjeA gene, encoding a novel deoxyribonuclease, from Bacillus subtilis. J Biochem. 142: 647-654.

22.     Gao, Q.T., Cheung, J.K., Li, J., Jiang, Z.Y., Chu, G.K., Duan, R., Cheung, A.W., Zhao, K.J., Choi, R.C., Dong, T.T.X. and Tsim, K.W.K. (2007): A Chinese herbal decoction, Danggui Buxue Tang, activates extracellular signal-regulated kinase in cultured T-lymphocytes. FEBS Lett. 581: 5087-93.

23.     Dong, X.B., Li, J., Jiang, Y., Zheng, Y., Dong, T.T.X., Tu, P.F. and Tsim, K.W.K. (2007): Determination of tenuifolin in tianwang buxinwan and guipiwan by HPLC. Zhongguo Zhong Yao Za Zhi. 32: 1647-1649.

24.     Gao, Q., Li, J., Cheung, J.K., Duan, J., Ding, A., Cheung, A.W., Zhao, K., Li, W.Z, Dong, T.T.X. and Tsim, K.W.K. (2007): Verification of the formulation and efficacy of Danggui Buxue Tang (a decoction of Radix Astragali and Radix Angelicae Sinensis): an exemplifying systematic approach to revealing the complexity of Chinese herbal medicine formulae. Chin Med. 2: 12.

25.     Gao, Q.T., Cheung, J.K., Choi, R.C., Cheung, A.W., Li, J., Jiang, Z.Y., Duan, R., Zhao, K.J., Ding, A.W., Dong, T.T.X. and Tsim, K.W.K. (2008): A Chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis induces the expression of erythropoietin in cultured Hep3B cells. Planta Med. 74: 392-395.

26.     Li, J., Li, W.Z., Huang, W., Cheung, A.W., Bi, C.W., Duan, R., Guo, A.J., Dong, T.T.X. and Tsim, K.W.K. (2009) Quality evaluation of Rhizoma Belamcandae (Belamcanda chinensis (L.) DC.) by using high-performance liquid chromatography coupled with diode array detector and mass spectrometry. J Chromatogr A. 1216: 2071-2078.

27.     Choi, R.C., Gao, Q.T., Cheung, A.W., Zhu, J.T., Lau, F.T., Li, J., Li, W.Z., Chu, G.K., Duan, R., Cheung, J.K., Ding, A.W., Zhao, K.J., Dong, T.T.X. and Tsim, K.W.K. (2009) A Chinese herbal decoction, Danggui Buxue Tang, stimulates proliferation, differentiation and gene expression of cultured osteosarcoma cells: genomic approach to reveal specific gene activation. Evid Based Complement Alternat Med. (Published online)

28.     Li, W.Z., Li, J., Bi, C.W., Cheung, A.W., Huang, W., Duan, R., Choi, R.C., Chen, I.S., Zhao, K.J., Dong, T.T.X., Duan, J.A. and Tsim, K.W.K. (2009) Can Rhizoma Chuanxiong replace Radix Angelica Sinensis in the traditional Chinese herbal decoction Danggui Buxue Tang? Planta Med. (Published online)

29.   Guo, A.J., Choi, R.C., Cheung, A.W., Li, J., Chen, I.X., Dong, T.T., Tsim, K.W.K., Lau, B.W. (2009) Stimulation of Apolipoprotein A-IV expression in Caco-2/TC7 enterocytes and reduction of triglyceride formation in 3T3-L1 adipocytes by potential anti-obesity Chinese herbal medicines. Chin Med. (Published online)

 

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