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Ma, Che Alex 馬徹

MaC 6x7副研究員 / 化學生物學組執行長


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Telephone: 02-27871233
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EDUCATION AND POSITIONS HELD:

  • B.S., Chemistry, National Taiwan University, 1992
  • M.S., Chemistry, University of Pennsylvania, 1996
  • Ph.D., Chemistry, University of Pennsylvania, 2000
  • Postdoctoral Fellow, University of California at San Diego, 2001
  • Postdoctoral Fellow, The Scripps Research Institute, 2001–2004
  • Assistant Research Fellow, Genomics Research Center, Academia Sinica, Taiwan, 2004-2010
  • Associate Research Fellow, Genomics Research Center, Academia Sinica, Taiwan, 2010- present
  • Visiting Scientist, RIKEN SPring-8 Center, Japan, 2016 – present
  • Division Director of Chemical Biology, GRC, Academia Sinica, Taiwan, 2016 – present

HONORS:

  • University of Pennsylvania, Teaching Assistant Award, 1995
  • Keystone Symposia Scholarship, Frontiers of Structural Biology, 2003
  • The Skaggs Postdoctoral Fellowship, 2001–2003
  • TWAS Young Affiliate, 2009-2013
  • Academia Sinica Significant Research Achievements, 2009
  • Academia Sinica Research Award for Junior Research Investigators, 2010
  • Two research highlights in Taiwan Yearbook of Technology, 2010
  • The Young Scholar Award of Tien-De Li Biomedical Foundation, 2011
  • Academia Sinica Significant Research, 2012
  • Academia Sinica Career Development Award, 2013
  • Exceptional Merit in Academic Award from Chung Hwa Rotary Educational Foundation, 2014
  • Taiwan Bio-Development Foundation Chair in Biotechnology, 2014

RESEARCH INTERESTS:

Structure of membrane proteins in drug discovery

The research focus of our laboratory is to study the structure and function of membrane proteins, and to understand their relationships in human diseases. Major efforts have been made over the last few years into the two topics in infectious diseases. First, in order to overcome the problems of drug-resistant bacterial infection, a new enzyme target for antibiotic development, the membrane-bound bifunctional transglycosylase, has been chosen for structural and functional analysis. We have successfully determined the X-ray crystal structure of this membrane-bound enzyme in complex with its inhibitor moenomycin, and studied its mechanism of peptidoglycan synthesis. In addition, a high-throughput screening method for finding new antibiotics has been developed using the purified full-length membrane protein. In parallel, structure-based drug design with our crystal structure is ongoing. Second, we have studied the effect of glycosylation on influenza virus major surface protein hemagglutinin (HA) with regards to its role in receptor binding and immune response, and developed a new strategy for molecular vaccine design.

figure copy-smallStructure of PBP1b-moenomycin complex provides critical information for new antibiotic development.

膜蛋白結構生物學與新藥研發

我們的研究重點是使用x光結晶學以及核磁共振光譜學來探討膜蛋白的結構。膜蛋白是使細胞能夠正常運作的重要組成之一,它們負責細胞內外像是離子傳導、分子傳輸、以及訊息接受等等的重要工作。膜蛋白的正常運作對於我們的健康非常重要,異常的膜蛋白與許多嚴重疾病有密切的關係。我們希望運用x光結晶學來決定具有醫療重要性的膜蛋白之結構。核磁共振光譜學將有助於針對這些結構的新藥開發。

RESEARCH HIGHLIGHTS:

SELECTED PUBLICATIONS:

  • Chen CL, Hsu JC, Lin CW, Wang CH, Tsai MH, Wu CY, Wong CH, Ma C, 2017, “Crystal Structure of a Homogeneous IgG-Fc Glycoform with the N-Glycan Designed to Maximize the Antibody Dependent Cellular Cytotoxicity.”, ACS chemical biology, 12(5),1335-1345. (SCI)
  • Chen CP, Lin MH, Chan YT, Chen LC, Ma C, Fischer WB, 2016, “Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization.”, Scientific reports, 6, 28866. (SCI)
  • Wu HH, Hwang-Verslues WW, Lee WH, Huang CK, Wei PC, Chen CL, Shew JY, Lee EY, Jeng YM, Tien YW, Ma C, Lee WH, 2015, “Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines.”, The Journal of experimental medicine, 212(3), 333-349. (SCI)
  • Huang CK, Yang CY, Jeng YM, Chen CL, Wu HH, Chang YC, Ma C, Kuo WH, Chang KJ, Shew JY, Lee WH, 2014, “Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-kappaB-mediated antiapoptotic pathway.”, Oncogene, 33, 2968-2977. (SCI)
  • Chen PC, Chuang PK, Chen CH, Chan YT, Chen JR, Lin SW, Ma C, Hsu TL, Wong CH, 2014, “Role of N-linked glycans in the interactions of recombinant HCV envelope glycoproteins with cellular receptors.”, ACS chemical biology, 9(7), 1437-1443. (SCI)
  • Kung CC, Naik MT, Wang SH, Shih HM, Chang CC, Lin LY, Chen CL, Ma C, Chang CF, Huang TH, 2014, “Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain.”, The Biochemical journal, 462(1), 53-65. (SCI)
  • Chen JR, Yu YH, Tseng YC, Chiang WL, Chiang MF, Ko YA, Chiu YK, Ma HH, Wu CY, Jan JT, Lin KI, Ma C, Wong CH, 2014, “Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections.”, Proceedings of the National Academy of Sciences of the United States of America, 111(7), 2476-2481. (SCI)
  • Chia-Ying Huang, Hao-Wei Shih, Li-Ying Lin, Yi-Wen Tien, Ting-Jen Rachel Cheng, Wei-Chieh Cheng, Chi-Huey Wong*, and Che Ma*, 2012, “Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism”, Proceedings of the National Academy of Sciences of the United States of America, 109(17), 6496-6501. (SCI)
  • Shih HW, Chang YF, Li WJ, Meng FC, Huang CY, Ma C, Cheng TJ, Wong CH, Cheng WC, 2012, “Effect of the peptide moiety of Lipid II on bacterial transglycosylase.”, Angewandte Chemie-International Edition, 51(40), 10123-10126. (SCI)
  • Chen JR, Ma C, Wong CH, 2011, “Vaccine design of hemagglutinin glycoprotein against influenza.”, Trends in biotechnology, 29, 426-434. (SCI)
  • M.-T. Sung, Y.-T. Lai, C.-Y. Huang, L.-Y. Chou, H.-W. Shih, W.-C. Cheng, C.-H. Wong and C. Ma*, 2009, “Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli”, Proceedings of the National Academy of Sciences of the United States of America, 106, 8824-8829. (SCI)
  • C.-C. Wang, J.-R. Chen, Y.-C. Tseng, C.-H. Hsu, Y.-F. Hung, S.-W. Chen, C.-M. Chen, K.-H. Khoo, T.-J. Cheng, Y.-S. E. Cheng, J.-T. Jan, C.-Y. Wu, C. Ma* and C.-H. Wong, 2009, “Glycans on influenza hemagglutinin affect receptor binding and immune response”, Proceedings of the National Academy of Sciences of the United States of America, 106, 18137-18142. (SCI)
  • T.-J. R. Cheng, M.-T. Sung, H.-Y. Liao, Y.-F. Chang, C.-W. Chen, C.-Y. Huang, L.-Y. Chou, Y.-D. Wu, Y.-H. Chen, Y.-S. E. Cheng, C.-H. Wong, C. Ma* and W.-C. Cheng, 2008, “Domain requirement of moenomycin binding to bifunctional transglycosylases and development of high-throughput discovery of antibiotics”, Proceedings of the National Academy of Sciences of the United States of America, 105, 431-436. (SCI)
  • Z. G. Zhang, C. Ma, O. Pornillos, X. Xiu, G. Chang and M. H. Saier, Jr., 2007, “Functional characterization of the heterooligomeric EbrAB multidrug efflux transporter of Bacillus subtilis”, Biochemistry, 46, 5218-5225. (SCI)
  • Y. J. Chen, O. Pronillos, S. Lieu, C. Ma, A. P. Chen and G. Chang, 2007, “X-ray structure of EmrE supports dual topology model”, Proceedings of the National Academy of Sciences of the United States of America, 104, 18999-19004. (SCI)
  • C. Ma and G. Chang, 2004, “Crystallography of the integral membrane protein EmrE from Escherichia coli”, Acta Crystallogr. D: Biol. Crystallogr., 60, 2399-2402. (SCI)
  • G. Veglia, A. C. Zeri, C. Ma and S. J. Opella, 2002, “Deuterium/hydrogen exchange factors measured by solution nuclear magnetic resonance spectroscopy as indicators of the structure and topology of membrane proteins”, Biophys. J., 82, 2176-2183. (SCI)
  • C. Ma, F. M. Marassi, D. H. Jones, S. K. Straus, S. Bour, K. Strebel, U. Schubert, M. Oblatt-Montal, M. Montal and S. J. Opella, 2002, “Expression, purification, and activities of full-length and truncated versions of the integral membrane protein Vpu from HIV-1”, Protein Sci., 11, 546-557. (SCI)
  • S. J. Opella, C. Ma and F. M. Marassi, 2001, “Nuclear magnetic resonance of membrane-associated peptides and proteins”, Methods in Enzymology, 339, 285-313.
  • C. Ma and S. J. Opella, 2000, “Lanthanide ions bind specifically to an added "EF-hand" and orient a membrane protein in micelles for solution NMR spectroscopy”, J. Magn. Reson., 146, 381-384. (SCI)
  • F. M. Marassi, C. Ma, H. Gratkowski, S. K. Straus, K. Strebel, M. Oblatt-Montal, M. Montal and S. J. Opella, 1999, “Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1”, Proceedings of the National Academy of Sciences of the United States of America, 96, 14336-14341. (SCI)