Project 3: Biological and Toxicological Assessment

Overview of Project

Exposure to particulate matter (PM) is currently associated with development of various respiratory diseases such as lung cancer, COPD, and asthma. Hallmarks of asthma include airflow obstruction, bronchial hyper-responsiveness, and airway remodeling. Particulate matter less than 2.5 µm in diameter (PM2.5) is derived mainly from industrial heating as well as the combustion of vehicle fuels and is considered to have clinical relevance since it deposits in the respiratory bronchioles of the lungs.  PM2.5 has been associated with premature mortality. Recent studies suggest an association between acute exposure to PM and daily mortality and morbidity, which was strongest for respiratory- and cardiovascular-related hospital admissions and cause of death in susceptible individuals. The Project 3 Team aims to complete these specific objectives across the three phases of the Center program: 

  • Characterize secretion of inflammatory cytokines/chemokines in human bronchial epithelial cells induced by PM;
  • Characterize airway inflammation in murine models of lung inflammation induced by bioavailable PMs;
  • Evaluate the role of ROS in PM-induced in vitro and in vivo airway inflammation and toxicity;
  • Link in vitro and in vivo gene expression patterns induced by PM with morbidity and mortality rates of the city where the sample was collected;
  • Link fluctuations in ambient bioavailable PM levels with relevant biomarkers (cytokines, epithelial/endothelial activation, peripheral blood mononuclear cell gene expression, exhaled breath condensates) in a panel of PM exposed human subjects;
  • Characterize signaling mechanisms of PM-induced secretion of inflammatory cytokines/chemokines and ROS burden in human bronchial epithelial cells.

Research in Progress:

Current research can be viewed in the annual Progress Reports:

Year1 Progress Report

Year 2 Progress Report

Selected Publications:

Published articles detailing the work of Project 3 can be viewed under Publications.

   

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