page last updated:
February 4, 2013
Department of Chemistry
532 Regents Hall
and O Streets NW
B.S. 1968, National Taiwan
Research Associate, The Rockefeller University, 1973-75.
I, Experimental Methods in Biochemistry,
Structure of Macromolecules,
1. RNA-protein interactions: Transfer
RNA and tRNA synthetases are two families of macromolecules
that translate the universal genetic code from nucleotide
based information to amino acid sequences. The kinetics,
the enzyme mechanism, the recognition, and their evolution
have provided a number of new and fundamental biochemical
principles. Bending of the 3’-end of tRNA upon
binding of synthetase, the assembly of mammalian
tRNA synthetases as a multi-enzyme complex, channeling
of tRNA from synthetase to the elongation factor,
and binding of tRNA by peptide from the extension
of mammalian synthetases have been elucidated in our
laboratory using fluorescence spectroscopy, circular
dichroism, single-turnover kinetics, and recombinant
2. Enzymatic modifications of proteins: Ubiquitin
is a highly conserved 76-amino acid protein and can be
enzymatically attached to numerous proteins such as transcription
factors, cell surface receptors, cell cycle regulators,
and stress proteins. Similar reactions have been found
with a number of ubiquitin-like proteins. Such modifications
alter the activities and stability of the substrate proteins;
thus, ubiquitination plays major regulatory roles in
cell cycle, transcription, stress responses, and signaling.
Taking advantage of the robust ubiquitin structure, we
are developing methods for the expression and purification
of proteins at the genomic scale for functional studies
of proteins and protein-protein interactions, isolating
and identifying protein substrates, characterizing structures
of modified proteins.
3. Gene expression alterations by bacterial toxins: Bacterial toxins such
as anthrax toxin bind to mammalian cells and drastically modify the host signaling
pathways or metabolism, eventually alter the gene expression, and some can be
used as biological threat agents. More sensitive and timely diagnostic methods
are required to combat the threats of biological weapons. Using cDNA microarrays,
we are identifying and quantifying the alterations of gene expression at the
nucleic acid and protein levels, their time dependence, and dose-responses. The
results are analyzed using bioinformatics, categorized to develop new diagnostic
methods, and synthesized for better understanding of the signaling mechanisms
through the use of toxins.
"Two Protein Lysine Methyltransferases Methylate Outer Membrane Protein B from Rickettsia" Abeykoon, A. H., Chao, C.-C., Wang, G., Gucek, M., Yang, D. C. H. & Ching, W.-M. Journal of Bacteriology (2012) 194, 6410-6418.
"Transcriptome characterization of immune suppression from battlefield-like stress" Muhie, S., Hammamieh, R., Cummings, C., Yang, D. & Jett, M. Genes Immun. (2013) 14, 19-34.
"FAT10 modifies p53 and upregulates its transcriptional activity" Li, T., Santockyte, R., Yu, S., Shen, R.-F., Tekle, E., Lee, C. G. L., Yang, D. C. H. & Chock, P. B. Archives of Biochemistry and Biophysics (2011) 509, 164-169.
“Identification and Biochemical Characterization of Small-molecule Inhibitors of Clostridium botulinum Neurotoxin Serotype A” Virginia Roxas-Duncan, Istvan Enyedy, Vicki A. Montgomery, Vanessa S. Eccard, Marco A. Carrington, Huiguo Lai, Nizamettin Gul. David C. H. Yang, and Leonard A. Smith; Antimicrobial Agents and Chemotherapy (2009) 53, 3478-86 [PubMed]
“Quinolinol and Peptide Inhibitors of Zinc Proteases in Botulinum Neurotoxin A: Effects of Zinc ion and Peptides on Inhibition” Lai, H.; Feng, M.; Roxas-Duncan, V.; Dakshanamurthy, S.; Smith, L. A.; Yang, D. C. H.; Archives of Biochemistry and Biophysics (2009) 491, 75-84 [PubMed]