| An increasingly large number of clinical, genetic studies have associated the cell-cell adhesion protein alpha-T-catenin with a diverse array of diseases, ranging from occupational and atopic asthma to autism spectrum disorder and Alzheimer's disease. However, it was unknown how alpha-T-catenin, which had previously only been described in the heart and testis, was able to contribute to the pathogenesis of all these diseases and disorders. For the diseases of the lung, I have shown that alpha-T-catenin is absent from the tissues of the airway, and instead is present only in the cardiac cells that surround pulmonary veins. From a murine model, mice lacking alpha-T-catenin show altered lung mechanics, suggesting that cardiac cell function in the lung may contribute to overall lung function. Furthermore, using different murine models of asthma, we have found that alpha-T-catenin contributes significantly to both occupational and atopic asthma. Interestingly, this effect was through regulation of pulmonary vein inflammation, which I found were an underappreciated contributor to allergic airway inflammation. In the brain, I found that alpha-T-catenin is absent from the neurons of the cerebrum, but instead could only be detected in the ependymal cell layer that lines the ventricles, as well as in the molecular layer of the cerebellum. The loss of alpha-T-catenin from these structures induced an increase in other cell-cell adhesion proteins, indicating alpha-T-catenin's cell-specific role in brain. Overall, I have shown that not only does alpha-T-catenin contribute to diverse diseases of the lung and brain, it likely does so in specific tissue types, suggesting potentially novel pathogeneses. |
