My laboratory is focused on the cellular and molecular events that are involved in the pathogenesis of injury and repair in the lung. We are particularly interested in the responses in human lung diseases and animal models of these diseases including asthma, chronic obstructive lung disease, pulmonary fibrosis and acute lung injury. Our studies have defined the cellular sources, regulation and effector profiles of many inflammatory, anti-inflammatory and remodeling cytokines in the lung including IL-1, IL-6, IL-11, leukemia Inhibitory factor, transforming growth factor-beta, vascular endothelial cell growth factor, IL-13 and gamma-interferon. These studies highlighted the cytokine networks that regulate their production, the transcriptional and post-transcriptional mechanisms that mediate these events, and their regulation by important respiratory states such as aeroallergen challenge, virus infection, innate immune activation and Th2 inflammation. In recent years, our lab has pioneered the use of lung specific constitutive and inducible overexpression transgenic mice to address the effector responses of these lung disease relevant genes. A recent refinement of this methodology utilizes triple transgenic methods to allow an investigator to control the timing of the expression of otherwise fetal-lethal transgene. By characterizing these mice we have been able to identify and are now studying many of the novel genes that are downstream of these moieties including chitinases and chitinase-like proteins, semaphorins, antiviral genes like MAVS and regulators of apoptosis. Whenever possible, findings in mice are taken directly to serum, plasma, DNA and tissue samples from well defined cohorts of human patients with these disorders and compared to appropriate controls.
Specialized Terms: Cell and Molecular biology of lung injury and repair; Asthma; COPD; Pulmonary fibrosis; acute lung injury; Cytokines; Inflammation; Internal Medicine; Pulmonary Diseases; Transgenic mice; genetically modified mice; Emphysema; Fibrosis; Inflammation
Asthma; Emphysema; Fibrosis; Inflammation; Internal Medicine; Lung; Pulmonary Fibrosis; Cytokines; Pulmonary Disease, Chronic Obstructive; Lung Injury; Acute Lung Injury