NRSA

	Anna Lam, MD
	Dr. Lam's research focuses on the mechanisms of stretch-enhanced gene delivery in alveolar epithelial cells. Cyclic stretch in lung epithelial cells causes a variety of responses, including increased gene transfer and expression following transfection. This increased gene transfer appears to be at the level of intracellular trafficking, perhaps related to the enhanced transcription factor expression and activation seen in stretched lung cells. Dr. Lam hypothesizes that cyclic stretch increases the levels of transcription factors and the binding of these factors to plasmid DNA, thus facilitating increased nuclear import of the DNA. This proposal will evaluate 1) the effect of cyclic stretch on the formation of plasmid-transcription factor complexes in the cytoplasm, 2) whether blocking the activation of transcription factors diminishes gene transfer in stretched lung epithelial cells, and 3) if stretch-activated transcription factors alone are sufficient to confer the same degree of stretch-enhanced gene delivery in unstretched lung epithelial cells. At the completion of these experiments, new insights will be gained into the mechanism of stretch-enhanced gene transfer, a promising technique for gene therapy in the injured lung.

	Krishna Thavarajah, MD
	Dr Tavarajah's research focuses on the association between exposure to air pollution and cardiac and respiratory health. Variation in the levels of a component of air pollution, particulate matter (a mixture of particles and liquid droplets), correlate with an increase in asthma and COPD exacerbations and cardiac events. She has shown that particulate matter-exposed macrophages induce fibroblast to myofibroblast transformation, a key phenotypic change of airway remodeling which can lead to irreversible airway disease. Dr Thavarajah hypothesizes that particulate matter induces airway remodeling via oxidant-mediated macrophage release of cytokines that trigger myofibroblast differentiation. Exploring the mechanisms of particulate matter-induced airway remodeling is important in providing preventative and therapeutic targets that apply to a broad range of patients.