Phenols are ubiquitous components of the human environment. The broad objectives of this research program are to determine the chemical and biochemical processes controlling the balance between their carcinogenic and anticarcinogenic properties. The central hypothesis is that phenolic compounds can form DNA lesions, containing an O-linked aryl group at the C8 position of purine nucleosides, which may contribute to cancer etiology. To develop the chemical tools needed to address these issues, the specific aims of this proposal are: (1) Develop a synthetic approach to phenol-substituted purine nucleoside analogs modified at C8; (2) Synthesize oligonucleotides containing O-linked phenol adducts and determine their stability; and (3) Develop an analytical method for the detection of O-linked phenol adducts and characterize the relationship between phenol activation and adduct formation. The results of this study can be important for evaluating the role of phenols in cancer, developing biomarkers of exposure, generating environmental regulatory guidelines, and establishing concepts important for phenol-based chemoprevention. The candidate will become (July, 2004) an assistant professor of Medicinal Chemistry at the University of Minnesota with an appointment in the Cancer Center. She holds a Ph.D. in Chemistry from MIT, where her research focused on organic synthesis. As an American Cancer Society postdoctoral fellow, the focus shifted to carcinogenesis and chemoprevention. The candidate has been presented with diverse opportunities for professional development through participation in collaborative research, supervising students, grant-writing, departmental service, teaching, and scientific conferences. Immediate career goals include transitioning to an independent faculty position and initiating a research program based on the union of synthetic organic chemistry with the study of carcinogenic mechanisms. The long-term career objective is to foster a rigorously active research group investigating initiation of cancer by environmental agents, diagnostic tools for carcinogen exposure, and prevention methods. The research career development plan is a phased program - a mentored period designed to strengthen the candidate's cancer research skills and professional development, and an independent phase to transition the research to the independent laboratory. The research environment presents faculty expertise and major instrumentation ideally suited for the proposed work.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Scientist Development Award - Research & Training (K01)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Ojeifo, John O
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University of Minnesota Twin Cities
Schools of Pharmacy
United States
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Kowal, Ewa A; Lad, Rahul R; Pallan, Pradeep S et al. (2013) Recognition of O6-benzyl-2'-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction. Nucleic Acids Res 41:7566-76
Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher et al. (2011) Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA. Nucleic Acids Res 39:3988-4006
Dahlmann, Heidi A; Sturla, Shana J (2011) Synthesis of oxygen-linked 8-phenoxyl-deoxyguanosine nucleoside analogues. European J Org Chem 2011:
Liu, Xiaodan; Villalta, Peter W; Sturla, Shana J (2009) Simultaneous determination of inositol and inositol phosphates in complex biological matrices: quantitative ion-exchange chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 23:705-12
Dahlmann, Heidi A; Vaidyanathan, V G; Sturla, Shana J (2009) Investigating the biochemical impact of DNA damage with structure-based probes: abasic sites, photodimers, alkylation adducts, and oxidative lesions. Biochemistry 48:9347-59
Norton, Jolanna; Matsuo, Hiroshi; Sturla, Shana J (2009) Synthesis of deoxytetrahydrouridine. J Org Chem 74:2221-3
Sturla, Shana J (2007) DNA adduct profiles: chemical approaches to addressing the biological impact of DNA damage from small molecules. Curr Opin Chem Biol 11:293-9
Vaidyanathan, V G; Villalta, Peter W; Sturla, Shana J (2007) Nucleobase-dependent reactivity of a quinone metabolite of pentachlorophenol. Chem Res Toxicol 20:913-9
Gong, Jiachang; Vaidyanathan, V G; Yu, Xiang et al. (2007) Depurinating acylfulvene-DNA adducts: characterizing cellular chemical reactions of a selective antitumor agent. J Am Chem Soc 129:2101-11
Gong, Jiachang; Neels, James F; Yu, Xiang et al. (2006) Investigating the role of stereochemistry in the activity of anticancer acylfulvenes: synthesis, reductase-mediated bioactivation, and cellular toxicity. J Med Chem 49:2593-9

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