My research comprises a program of translational research and genomics in two common lung diseases, asthma and chronic obstructive pulmonary disease (COPD). These studies fall into three specific categories: 1) the identification of distinct molecular sub-phenotypes of asthma and COPD, 2) the…
more elucidation of mechanisms of airway inflammation and remodeling and 3) clinical trials of novel therapeutic approaches. My most prominent work has been the identification of markers of interleukin-13 (IL-13) driven inflammation in the lung (PNAS 2007), and the application of these markers to demonstrate clinically important molecular heterogeneity in asthma (AJRCCM 2009). Based on these studies, one of these markers, periostin, has proven to mark a distinct IL-13 high sub-phenotype of asthma and to identify patients with asthma who respond to lebrikizumab, a novel anti-IL13 antibody (Corren NEJM 2011). In other work, I study mechanism of airway remodeling in asthma through quantitative morphometry and gene expression studies in human bronchial biopsy specimens. This work has shown that airway smooth muscle remodeling accompanies even mild asthma and is characterized by an increase in smooth muscle cell number without cellular hypertrophy or change in phenotypic markers (AJRCCM 2004). Finally, I have applied functional genomics to human samples to identify mediators of macrophage recruitment and activation in COPD. Major findings include the identification of matrix metalloproteinase-12 (MMP12) induction in human COPD (AJRCCM 2005) and a role for DAP12-associated receptors in alveolar macrophage recruitment to the lung in human smokers and in mouse models of lung inflammation (JI 2010).
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