Dr. Yang's present research focuses on understanding the structures and functions of biologically relevant DNA G-quadruplex secondary structures, and their interactions with proteins and small molecules. DNA G-quadruplex secondary structures formed in specific G-rich sequences have recently emerged as a new class of cancer-specific molecular targets for cancer therapeutics, which is their long-term goal. One important feature of the DNA G-quadruplexes is that they are globularly folded nucleic acid structures which are uniquely determined by the primary nucleotide sequences up to 20-30 bases in length, in a manner analogous to protein folding from a primary amino acid sequence. Unlike the triplex DNA, DNA quadruplexes can readily form in solution under physiological conditions. their primary approach, high-field NMR spectroscopy, represents a major tool for determination of DNA secondary structures under physiological conditions, due to the difficulty of crystallization of such structures. DNA G-quadruplexes formed in the promoter regions have been suggested to be transcriptional regulator for a number of important oncogenes, including c-MYC, bcl-2, PDGFR-b, VEGF, and HIF-1. their group has made significant contributions in the G-quadruplex field. They have determined the major G-quadruplex structure formed in the human c-MYC and bcl-2 promoters, the first two promoter G-quadruplex structures determined.
They have also determined the physiologically relevant intramolecular telomeric G-quadruplex structure, which resolved the considerable controversy in the field caused by the crystal structure that does not appear to form in K+ solution. Most recently, they have determined the first drug complex structure of an intramolecular promoter G-quadruplex.