Lab Research Interests:
Our studies focus on the mechanism by which environmental chemicals produce tissue selective toxicity in the respiratory system. The vast majority of the agents we work with undergo metabolic activation by the cytochrome P450 monooxygenases to reactive electrophiles which become bound covalently to proteins. Naphthalene and various naphthalene derivatives are the primary focus of our work. These compounds are pyrolysis products generated during combustion. Human exposure occurs as a result of lifestyle choices (cigarette smoking) as well as in industrial settings. In addition, naphthalene and nitronaphthalenes are found in ambient air samples. Naphthalene produces highly selective injury in murine but not in rat lungs thus raising the issue of the importance to the human. A number of avenues are being explored in an attempt to determine whether these chemicals represent a real risk to the human. In many of our studies, we are attempting to identify the precise mechanism by which the chemicals produce cytotoxicity with the view that once this is fully understood, we will be able to investigate the same processes in primate lungs. Another potential approach that we are exploring involves the development of biomarkers which are intimately associated with the metabolic and cellular mechanisms of toxicity. Much of this work involves identification of protein adducts and their degradation products.