Host Immune Response

The overall research interest is to elucidate mechanisms of immune tolerance versus inflammation as they relate to pulmonary diseases such as severe asthma as well as host-pathogen interactions in the respiratory mucosa. Early research from her lab led to the identification of NF-κB as a target for glucocorticoid-mediated repression of gene expression and the discovery of GATA-3 as a master regulator of Th2 cells, which promote allergic diseases including asthma. Her laboratory also identified a key role for Tregs expressing membrane-bound TGF-β with cross-talk with the Notch pathway in promoting immune tolerance in the airways. In a study published recently by her group, rather than a dominance of Th2/type 2 immune response, which is commonly associated with asthma, an IFN-γ/Th1 immune bias was detected in more than 50% of severe asthmatics. The heightened Th1 response was shown to inhibit expression of an important protease inhibitor, SLPI, by airway epithelial cells. This study also utilized a newly developed animal model of severe asthma established in her lab, which can be used to test novel therapeutics for severe asthma. In the context of immune tolerance, her recently published study has identified an important role of mitochondrial metabolism in lung dendritic cells in the maintenance of immune tolerance in the airways. Studies in her lab are conducted using animal models of disease and human samples, which are analyzed using cutting-edge immunological, molecular, biochemical, physiological and imaging techniques.