The genetic toxicology of inflammation and aging

The Dedon research group has a long-standing interest in understanding the link between chronic inflammation and human diseases, such as cancer. Activation of the innate immune system by infection or tissue damage leads to the generation of highly reactive oxygen and nitrogen species, such as nitric oxide (NO), superoxide (O2-), peroxynitrite (ONOO-), nitrosoperoxycarbonate (ONOOCO2-) and hydrogen peroxide (H2O2). Intended to combat an invading microbe, these reactive species also damage virtually all types of biological molecules in surrounding host cells. The working hypothesis is that these chemical mediators of inflammation cause cellular damage that eventually leads to the causative mutations of cancer.

Current projects in inflammation and chemical immunology embrace three areas. One involves development of damage products as biomarkers, with emphasis on developing ultrasensitive mass spectrometric methods to quantify RNA, DNA, protein and lipid damage. These biomarkers represent surrogates for the short-lived reactive oxygen and nitrogen species, as well as indices of the severity of the inflammatory process. The second research thrust involves metabolomic analyses of serum and urine for biomarkers of inflammation, using an LC-QTOF approach. The third area of research involves defining the chemical mechanisms of damage caused by reactive nitrogen and oxygen species, using a novel NO delivery system and mouse models of inflammation, colitis, gastritis and liver disease.