Asbestos-related lung diseases (asbestosis, bronchogenic lung cancer and mesothelioma) continue to pose serious health concerns worldwide, including in the veteran population. The pathogenesis of asbestos-induced lung diseases is incompletely understood. The proposed studies should provide insight into the molecular mechanisms underlying asbestos-induced alveolar epithelial cell (AEC) cell death (apoptosis), which is an important initial event leading to fibrosis and carcinogenesis. Specifically, we investigate the role of AEC mitochondria-derived ROS, p53 (Noxa) activation and down-stream Bax activation. These studies will also characterize the role of mitochondrial DNA repair enzyme (hOgg1) and aconitase in preventing asbestos-induced AEC apoptosis. Notably, the asbestos paradigm should provide insights into the pathogenesis of other more common diseases, such as lung cancer and idiopathic pulmonary fibrosis, which are frequently present in the veteran population and for which more effective management strategies are clearly needed.
|Effective start/end date||11/1/16 → 9/30/18|
- Jesse Brown VA Medical Center (Agmt 04/12/17)