The focus of my research involves the biophysical characterization of nucleic acid structures and stabilities as related to both base sequence effects as well as complex formation with small molecules and proteins. My initial research efforts focused on DNA as a target for small molecules such as anticancer agents including intercalating and groove binders and the mechanistic processes of molecular recognition. An understanding of the forces that govern DNA base sequence-specific interactions for small molecules and/or proteins is fundamental towards our comprehension of basic processes associated with gene expression such as transcription, recombination, DNA repair, as well as the recognition of DNA cleavage sites for nuclear enzymes such as topoisomerase I and topoisomerase II.
More recently, our research has focused on the structural, stability, and protein-binding properties of G-quadruplex DNA fragments. Recent studies in my laboratory have demonstrated that small deoxyribonucleotides can act as modulators of a number of toll-like receptor (TLR) mediated biological responses, including cancer cell invasion. Although the nature of the TLR9-mediated cell invasion is not understood, the key determinant seems to reside in the stable nuclease-resistant structure(s) of the oligonucleotides either for binding to the target protein or protection from nuclease invasion. We continue to use a multifaceted approach of calorimetry and high-resolution NMR to discern the structure and stability of nucleic acids and protein-nucleic acid complexes.
