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Research

Our laboratory focuses on two main research program. (1) Studying the effects of cigarette smoke (CS) exposure in the pathogenesis of airway and lung diseases such as chronic obstructive pulmonary disease (COPD) using preclinical genetic mouse models and human biosamples. (2) Studying novel immune regulators in the lung during respiratory infections. (3) Translating basic research findings in human patient population.

COPD

COPD is a composite entity that includes chronic bronchitis and emphysema, is a leading cause of death in the world, and is a disease that is in need of new treatments. One of the goal of our laboratory is to investigate the interaction between CS and respiratory virus infection in the pathogenesis of COPD and identify novel therapeutic targets for this respiratory disease. It has been long thought that the frequent respiratory infections in COPD patients are due to their depressed immune function.

Our studies have revealed that CS-exposed hosts have an over-exaggerated immune reaction to viral infections. Frequent acute COPD exacerbations correlate with increased rate of disease progression and more loss of lung function in COPD especially if it is due to viral infections. Our studies have shown that CS exposure has an impressive ability to regulate the innate immunity in the lung after influenza virus and respiratory syncytial virus (RSV) infection. CS enhances the inflammation, alveolar destruction and airway fibrosis caused by influenza virus and RSV. These effects are mediated by type I interferon and RIG-like helicase antiviral innate immune pathway. CS exposure also results in the induction of interleukin-15 in the setting of these respiratory infections.

We hypothesize that these novel mechanistic pathways may explain the heightened inflammatory response and worsening lung functions in COPD patients with multiple virally-induced exacerbations, and the chronic lung inflammation seen in stable COPD patients. We have also translated our findings by studying these immune mediators in patients infected with various respiratory viruses and have thus far collected >200 human biosamples.