Natalia Tretyakova
| Natalia Tretyakova, Ph.D. Office: Office Telephone Number: Lab Telephone Number: E-mail Address: Research Group Web site |
EDUCATION:
B.Sc. / M.S. Moscow State University, 1990
Ph.D. University of North Carolina at Chapel Hill, 1997
Postdoctoral Massachusetts Institute of Technology
RESEARCH INTERESTS:
Our laboratory uses a combination of organic synthesis, structural analysis, and bioanalytical methods to characterize DNA and protein adducts of chemical carcinogens and drugs. Humans are exposed to complex mixtures of environmental and dietary carcinogens, as well as endogenous electrophiles produced from normal metabolism. Some of these chemicals and their metabolites are capable of chemical reactions with cellular biomolecules. Many common antitumor drugs including nitrogen mustards, platinum compounds, and alkylnitrosoureas kill tumor cells by inducing toxic DNA lesions. The focus of our research is to investigate the structural basis for carcinogenic and anticancer activity of DNA- and protein-modifying agents. Synthetic methodologies are developed to prepare structurally modified nucleosides and amino acids representing carcinogen- and drug-induced DNA and protein adducts. The effects of nucleobase modifications on DNA structure and stability are determined by NMR, CD spectroscopy, and computer modeling of chemically altered DNA. Biological mass spectrometry techniques are employed to quantify the formation of DNA and protein adducts in vivo. These studies identify the molecular targets of exogenous and endogenous electrophiles and provide an insight into the origins of their biological activity.
RECENT PUBLICATIONS
Tretyakova, N., Guza, R., and Matter, B. (2008) Endogenous cytosine methylation and the formation of carcinogen-DNA adducts. Nucleic Acid Symp. Ser. 52, 49-50.
Goggin, M., Swenberg, J.A., Walker, V., and Tretyakova, N.Y. (2009) Molecular dosimetry of 1,2,3,4-diepoxybutane-induced DNA-DNA cross-links in B6C3F1 mice and F344 rats exposed to 1,3-butadiene by inhalation. Cancer Res. 69, 2479-2486.
Moser, A., Guza, B., Tretyakova, N.Y., and York, D. (2009) Density functional study of the influence of C5 cytosine substitution in base pairs with guanine. Theor. Chem. Accounts. 122, 179-188.
Loeber, R., Michaelson, E., Fang, Q., Campbell, C., Pegg, A.E., and Tretyakova, N. (2008) Cross-linking of the DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem. Res. Toxicol. 21, 787-795.
Goggin, M., Anderson, C., Park, S., Swenberg, J., Walker, V., and Tretyakova, N. (2008) Quantitative HPLC-ESI+-MS/MS of the adenine-guanine cross-links of 1,2,3,4-diepoxybutane in tissues of butadiene-exposed B6C3F1 mice. Chem. Res. Toxicol. 21, 1163-70.
Tretyakova, N., Livshits, A., Park, S., Bisht, B., and Goggin, M. (2007) Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Chem. Res. Toxicol. 20, 284-289.
Guza, R., Ma, L., Fang, Q., Pegg, A.E., and Tretyakova, N.Y. (2009) Cytosine methylation effects on the repair of O6-methylgunaines within CG dinucleotides. J. Biol. Chem. 284, 22601-22610.