David Chih Hsin Yang
Office: 532 Regents Hall
B.S. 1968, National Taiwan Universit
Ph.D. 1973, Yale University
Research Associate, The Rockefeller University, 1973-75.
Biochemistry I, Experimental Methods in Biochemistry, Structure of Macromolecules, Enzyme Kinetics
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 DNA.
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.
Structural Insights into Substrate Recognition and Catalysis in OmpB by Protein Lysine Methyltransferases from Rickettsia. (2016)
A. H. Abeykoon, N. Noinaj, B.-E. Choi, L. Wise, Y. He, C.-C. Chao, G. Wang, M. Gucek, W.-M. Ching, P. B. Chock, S. K. Buchanan, D. C. H. Yang Journal of Biological Chemistry 291 19962-19974
Multimethylation of Rickettsia OmpB Catalyzed by Lysine Methyltransferases (2014) A. Abeykoon, G. Wang, C.-C. Chao, P. B. Chock, M. Gucek, W.-M. Ching and D. C. H. Yang Journal of Biological Chemistry 289 7691-7701
Transcriptome Chracterization of Immune Suppression from Battlefield-like Stress (2013) S. Muhie, R. Hammamieh, C. Cummings, D. C. Yang and M. Jett Genes and Immmunity 14 19-34
Two Protein Lysine Methyltransferases Methylate Outer Membrane Protein B from Rickettsia (2012) A. H. Abeykoon, C.-C. Chao, G. Wang, M. Gucek, D. C. H. Yang and W.-M. Ching Journal of Bacteriology 194 6410-6418
Identification and Biochemical Characterization of Small-Molecule Inhibitors of Clostridium botulinum Neurotoxin Serotype A (2009) V. Roxas-Duncan, I. Enyedy, V. A. Montgomery, V. S. Eccard, M. A. Carrington, H. G. Lai, N. Gul, D. C. H. Yang and L. A. Smith Antibimicrobial Agents and Chemotherapy 53 3478-3486
Polyubiquitylation of PARP-1 through ubiquitin K48 is modulated by activated DNA, NAD+, and dipeptides (2008) T. Wang, C. M. Simbulan-Rosenthal, M. E. Smulson, P. B. Chock and D. C. H. Yang Journal of Cellular Biochemistry 104 318-328