Professor; BA, Occidental College; MS and PhD, University of California,
San Diego; Damon Runyon-Walter Wincell Cancer Fund Postdoctoral Fellow;
NSF Presidential Young Investigator Award; Camille and Henry Dreyfus Teacher-Scholar
Award; Genn T. Seaborg Research Award.
We are interested in nucleic acid structure and sequence specific recognition of nucleic acids by proteins, peptides, and drugs. Our primary research tool is multidimensional, multinuclear nuclear magnetic resonance (NMR) spectroscopy. These techniques are used to determine the three-dimensional structures of DNA and RNA oligonucleotides, to investigate their interactions with various proteins and drugs, and to study nucleic acid folding.
Much of our research is on unusual nucleic acid structures. These include DNA and RNA triplexes and quadruplexes and aptamers. Triplexes are formed by binding of a third strand of DNA or RNA in the major groove of Watson-Crick duplex DNA. Triplexes are of interest both for their potential use as therapeutic agents to repress gene expression and their proposed formation in vivo as H-DNA. Quadruplexes are formed when four guanine-rich strands associate via formation of Hoogsteen bonded G-quartets. Formation of quadruplexes has been proposed for the G-rich 3' single strand overhangs of telomeres, immunoglobulin switch regions, and dimerization of HIV genomic RNA. Aptamers are DNA or RNA ligands which have been selected from a random pool of oligonucleotides for their ability to bind a specific substrate. An example is a DNA 15mer which binds to and inhibits thrombin.
We are also studying a part of the rev responsive element (RRE) of the HIV RNA genome which binds the Rev protein. Mutant RREs, RRE-Rev peptide, and RRE-Rev protein studies are in progress. Other projects include studies of sequence specific interactions of a variety of drugs with DNA. Future projects will include complexes of DNA and RNA binding proteins to nucleic acids.
Biochemistry: nucleic acid structure; DNA triplexes; DNA quadruplexes; nucleic acid-drug complexes; RNA structure; RRE-Rev interactions; nucleic acid-protein complexes; RNA and DNA aptamers; peptide folding; multidimensional nuclear magnetic resonance spectroscopy.