Research

Background and Research Focus

Dr. Lee’s laboratory has been focused to develop transgenic animal models (transgenic and null mutant KO mice) to investigate the in vivo role and effector function of cytokines and mediators in the pathogenesis of asthma, acute lung injury, pulmonary vascular disease, pulmonary fibrosis and emphysema. Working in a close collaboration with Dr. Jack A Elias, a number of lung-specific transgenic and null mutant mice has been successfully generated and used by a number of investigators around the world. They include IL-10, VEGF, TGF-beta, IL-18, IL-15, Chi3l1/BRP-39, Chitotriosidase (Chitinase1) transgenic and null mutant mice.

Currently, our laboratory focus to define the molecular mechanism regulating pulmonary fibrosis and emphysema. Our laboratory made made significant progress in defining the role of chitinase and chitinase-like proteins (C/CLP) in the pathogenesis of allergic inflammation airway remodeling, fibrosis and lung injury. We are also intensively investigate the regulatory mechanism of tissue remodeling, fibrosis and emphysema, by TGF-beta, mainly using TGF-beta transgenic mice and cigarette-smoke (CS) exposure.

Although cigarette smoke is a common risk factor for the development of pulmonary fibrosis and emphysema, the mechanism underlying this divergent tissue response of CS exposure has not been clearly understood. Interestingly, we have found that the TGF-beta Tg mice in different genetic backgrounds demonstrated divergent tissue phenotypes of pulmonary fibrosis and emphysema. This observation led us to determine the genetic factors that modulate TGF-beta effector function. Through extensive haplotype analysis and mRNA expression arrays, we further defined potential genetic modifiers. Elucidation of the role and effector function of these genetic modifiers in the pathogenesis of emphysema and pulmonary fibrosis will be essential in understanding CS-induced pathologies as well as in developing therapeutic intervention of these devastating pulmonary diseases.

Current Projects

  1. Define the role of genetic modifiers in TGF-beta-induced pulmonary fibrosis and emphysema. 
  2. Define the role of Chi3L1 in the development and progression of primary and metastatic lung cancer. 
  3. Role of arginase 2 (Arg2) and IL-13R alpha 2 in the pathogenesis of pulmonary arterial hypertension.