PhD, Institute of Biophysics (1995)
Postdoctoral Associate, Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institutes
We study the molecular structure, function, and mechanism of proteins or complexes related to bacterial or viral infection and host response, using crystallography, biochemistry, and molecular biology. Current projects include bacterial and viral superantigens, signaling proteins involved in apoptosis and stem cell regulation, and rational drug design against key viral enzymes.
Bacterial and viral superantigens are functionally-related proteins that have the ability to stimulate the activation of large number of T cells bearing particular TCR Vß domains. We recently determined the first crystal structure of a complete ternary complex of a superantigen, TCR, and pMHC. The complex structure revealed that superantigen contacts not only the TCR ß chain but TCR Vα. This finding is in contrast to that of traditional superantigens which only recognize TCR ß chain. Future studies will focus on investigation of the role of TCR Vα in superantigen recognition and novel superantigens such as Crohn's disease-associated protein PfiT.
We also study the structure and mechanism of the essential enzymes encoded by West Nile virus (WNV). WNV, as an emerging infectious pathogen, is a new threat to the public health. The viral essential enzymes will be ideal targets for anti-viral drug designs. We have identified a dual function of the viral methyltransferase, which catalyzes both guanine N7 and ribose 2'-O methyl transfer reactions. We also determined its crystal structure. We will continue working on determining the mechanism of recognition of the RNA cap substrates by the methyltransferase. In the long-term, these findings may lead to development of specific therapeutics to treat WNV-associated diseases.
Other developmental projects include the structural and functional studies of a protein kinase and its interaction with signaling proteins involved in apoptosis, and transcription factors regulating stem cell growth.