Research Project: Learning How the Body Repairs Damaged Lung Epithelium
acute lung injury
The cells lining the lung form a protective layer called the epithelium, which must be repaired when it is damaged by air pollutants or other toxins. This repair is accomplished by inducing cell division to replace dead cells and cell migration to remodel airways. Occasionally, these cellular repair processes are overactive, can lead to fatal diseases such as lung cancer and pulmonary fibrosis. We will study how the repair induction signals between cells collaborate with a key metabolic regulator known as AMPK to ensure that the lung repair process is efficient and avoids the excessive responses that lead to disease. These findings will contribute to efforts to change cell behaviors to manage lung cancer, fibrosis, and other aging-related disorders of lung epithelial dysfunction.
We have developed a cellular imaging platform to track cell growth, metabolism, and danger signals in single living cells. We are using this tool to test how individual lung epithelial cells function as signaling units when they are exposed to disease-related situations, such as pathogens or inflammation. We have collected an extensive dataset on single-cell signaling behavior under a range of such conditions. Based on these datasets we are constructing quantitative models of cell communication functions. These models will reveal more precisely how abnormal signaling diverges from normal signaling, providing insight into disease processes and how signal-modulating drugs such as kinase inhibitors can be used to restore normal signaling.