Research Interests

My research interests are in structural biology of nucleic acids and their complexes. My laboratory has pioneered the application of macromolecular NMR spectroscopy to the study of DNA and RNA structure, folding, and interactions with cations, drugs, and proteins. Our work on Z-DNA, DNA triplexes, quadruplexes, and aptamers was seminal in defining the conformational variability of DNA. We solved the first high resolution structure of a DNA quadruplex, formed from the Oxytricha telomere repeat, which revealed a novel fold and set the standard for high resolution structures of nucleic acids determined by NMR. My laboratory has also developed new methods for studying cation binding to nucleic acids, and applied these to provide new insights into DNA A-tract bending. Much of our recent work has been focused on understanding RNA folding, including studies of RNA aptamers, ribozymes, riboswitches, and H/ACA RNA and recognition of RNA by proteins. Work from my laboratory has combined structural and functional studies of RNA-protein complexes to reveal essential determinants of protein recognition of both single stranded and double stranded RNA. The current major focus of my laboratory is on structural and functional studies of telomerase, the riboprotein complex responsible for maintenance of telomere ends. We identified a conserved triple helical region on the human telomerase RNA pseudoknot that is essential for catalysis and the sequence and structural requirements in the CR7 domain for localization to Cajal bodies and 3' end processing. This work has provided fundamental new insights into the role of telomerase RNA in telomerase function.

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Primary Section

Section 29: Biophysics and Computational Biology

Secondary Section

Section 21: Biochemistry