My research interests are mainly focused in three areas: 1) Understanding unfolding-mediated protein aggregation and polymerization using the gS-crystallin protein as a tractable model system. One hydrophobic mutation of this protein, Opj, exhibits a concentration and temperature-dependent protein aggregation. The progressive nature of Opj in vivo is similar to those mutations commonly detected in age-related cataracts. 2) Elucidating the mechanism of a novel family of nucleotide hydrolases. RCL is up-graduated by c-Myc oncogene, and proposed to serve as a nucleotide salvage pathway enzyme and/or promote angiogenesis in many tumor cells. Structural and kinetic studies indicated that RCL shares some similarity with the deoxynucleoside transferases, but more importantly possesses its novelty both in the structure and in its mechanism underlying the enzymatic catalysis. 3) Investigating the protein-nucleic acid and protein-protein interactions critical for gene regulation by the Gfi-1 transcription factor, which is a vital component in hematopoietic process. The six-zinc finger domain of Gfi-1 has been shown to be responsible for these interactions, and mutants within this domain are associated with AML. In my laboratory, we use nuclear magnetic resonance (NMR) in parallel with multiple biophysical methods to reveal detailed structural and dynamic information of these macromolecules to help providing fundamental insights into their functional mechanism in their related biological processes.
