Core A provides Project researchers with state-of-the-art analytical tools, techniques and experience in the characterization and quantitation of chemical substances and modifications of cellular molecules such as DNA, RNA, lipids, proteins and small-molecule metabolites. It also provides well-characterized cell lines and controlled delivery of nitric-oxide-related DNA and protein damaging agents to these cells to insure quality-control and reproducibility among the Projects. It operates as a service, a developmental laboratory, and as a resource for the Program. Individual researchers use the facilities as needed at three levels: as a service lab, for supervised analyses, or as fully trained users. In addition, we continually expand and improve our capabilities with the development and acquisition of technologies that facilitate the research programs.
Specific aims evolve yearly and typically include the development and improvement of Project-related analytical methods, evaluation of new hardware, and evaluation of recently-acquired or potentially useful software. For the year just ending, these were the development and improvement of project-related analytical methods (e.g., quantitation of modified tyrosines), exploitation evaluation of new hardware, and continued focus on targeted quantitation of peptides and proteins, e.g., using click-chemistry-based derivatization for sample enrichment. New equipment and expertise needs are identified in member surveys conducted by the Administrative Core and one-on-one discussions with Project leaders, and via Program- Project group meetings.
Inflammation is now recognized as a major factor in the etiology of many types of cancer. The proposed research will open new understanding of the role of the chemical changes to proteins and DNA brought about by the immune cells attracted to the site of inflammation. The overall chemical damage contributes strongly to the process leading to cancer.
|Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P et al. (2017) The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environ Mol Mutagen 58:508-521|
|Fedeles, Bogdan I (2017) G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress. Proc Natl Acad Sci U S A 114:2788-2790|
|Chang, Shiou-Chi; Seneviratne, Uthpala I; Wu, Jie et al. (2017) 1,3-Butadiene-Induced Adenine DNA Adducts Are Genotoxic but Only Weakly Mutagenic When Replicated in Escherichia coli of Various Repair and Replication Backgrounds. Chem Res Toxicol 30:1230-1239|
|Chen, Fangyi; Bian, Ke; Tang, Qi et al. (2017) Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. Chem Res Toxicol 30:1102-1110|
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|Chen, Fangyi; Tang, Qi; Bian, Ke et al. (2016) Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA. Chem Res Toxicol 29:687-93|
|Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B et al. (2016) S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration. Proc Natl Acad Sci U S A 113:4152-7|
|Peng, Chunte Sam; Fedeles, Bogdan I; Singh, Vipender et al. (2015) Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity. Proc Natl Acad Sci U S A 112:3229-34|
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