Our laboratory primarily focuses on understanding the complexity of DNA damage and DNA repair in living organisms. DNA damage is involved in numerous diseases such as cancer and may also be an important factor in the aging process. Oxidative damage to DNA caused by oxygen-derived free radicals is the most frequent type encountered by living cells. Free radicals are formed naturally in living cells by oxygen metabolism. These species are also produced in cells exogenously by the action of DNA-damaging agents. Exogenous sources include ionizing and ultraviolet radiations, redox-cycling drugs, chemical oxidants, carcinogenic compounds, and certain types of engineered nanomaterials. Oxidative damage to DNA produces a multiplicity of modifications in DNA including base and sugar lesions, strand breaks, DNA-protein cross-links, and base-free sites. Accurate measurement of these lesions is essential for the understanding of mechanisms of oxidative DNA damage, and its repair and biological effects. Our laboratory primarily uses mass spectrometric techniques such as gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and liquid chromatography/tandem mass spectrometry for the measurement of DNA damage. DNA damage is repaired in living cells by DNA repair enzymes. If not repaired, DNA damage may lead to detrimental biological consequences such as mutagenesis, carcinogenesis, and cell death. Mutations in specific genes may activate oncogenes or inactivate tumor suppressor genes, contributing to the various stages of carcinogenesis. Thus, DNA repair is regarded as one of the essential events in all life forms. Detailed knowledge of mechanisms of DNA damage and its repair might allow us to modulate DNA repair. This could lead to potential development of drugs for prevention and treatment of disease. Clinical applications of this approach may include the improvement of cancer therapy by inhibiting DNA repair in drug- or radiation-resistant tumors and/or the increase in the resistance of normal cells to DNA damage by overexpressing DNA repair genes. In a complementary area of research, our laboratory is also investigating and applying targeted metabolomics to characterize the intracellular toxicity and oxidative DNA damage/repair resulting from the interaction of biomedically-relevant nanomaterials (e.g., nanoparticles, quantum dots, carbon/silica nanotubes) with human cell lines.
Cancer; DNA; DNA repair enzymes; Free radicals; Gas chromatography/mass spectrometry; Liquid chromatography/tandem mass spectrometry; Nanomaterials and nanoparticles; Oxidative stress; Toxicity;