William D. Currie
Associate Professor Emeritus of Radiology
Our research interests remain focussed on the effect of environmental toxins on the pulmonary surfactant system and on the effect of low level ionizing radiation on the central nervous system.
Environmental atmospheric particle exposure has been linked to chronic airway obstructive disorders (CAOD) through epidemiological evidence. However we still do not understand the pathophysiological basis for the effect. Previous studies have indicated that alterations in pulmonary surfactant function can increase airflow resistance by the formation of fluid plugs in the narrow passages leading to the alveoli. We believe that particle exposure causes surfactant inhibitors to leak into the alveolar and bronchiolar lining fluid, thereby reducing gas exchange in the terminal airways and as a consequence exacerbating sub-clinical respiratory compromise in patients with CAOD. We have been working in collaboration with the Health Effects Research Laboratory of the United States Environmental Protection Agency. Through this collaboration, we have been studying the pulmonary toxicological effects of intratracheally instilled particles on BALB/c mice. These studies have been undertaken to characterize the effect of both industrial (residual oil fly ash) and environmental (Washingon DC ambient air) particles on the amount or activity of pulmonary surfactant inhibitors in the airway lining fluid. Using the bioassay developed in our laboratory to assess pulmonary surfactant function, we have recently demonstrated that acute particle exposure leads to a sustained increase in airway surfactant inhibitor activity. Our studies to date suggest that the surfactant inhibitors induced by particle exposure do not appear as the result of non-specific leakage of serum proteins, and, accordingly, may differ from those observed in association with adult respiratory distress syndrome (ARDS). We are continuing our efforts to define the molecular basis for the effect of particle exposure on the pulmonary surfactant system.
There are many clinical reports suggesting that ionizing radiation exerts a therapeutic effect in alleviating seizures, the mechanistic basis for this salutary effect is unknown. Surprisingly little experimental work has been performed to define the basis for seizure suppresion following CNS irradiation. A recent comprehensive review on the therapeutic efficacy of cerebral irradiation in epilepsy cited only two relevant studies in animals, both examining the effects of ionizing radiation in a chronic focal epilepsy model. We are currently studying the effects of charged particle beam radiation administered to the brain (hemispheric irradiation) on EEG activity. We have already shown that cerebral irradiation reduces the intrinsic susceptibility of the brain to paroxymal electrical discharges induced by alterations in glutaminergic and GABAergic neurotransmission. We are now developing analytical techniques for measuring the amount of excitatory neurotransmitters in the brain following exposure of the CNS to charged particle ionizing radiation. These studies are providing important information on the molecular basis for seizure suppression secondary to CNS irradiation and a scientific rationale for maximizing the clinical benefits of neuro-oncological radiotherapy and radiosurgical procedures.
Current Appointments & Affiliations
Education, Training, & Certifications
Some information on this profile has been compiled automatically from
Duke databases and external sources. (Our
About page explains how this works.)
If you see a problem with the information, please write to
Scholars@Duke and let us know. We will