The primary focus of the laboratory is the elucidation of the molecular and cellular mechanisms of lung injury (inflammation and fibrosis) from a diverse array of agents including bleomycin, silica, asbestos, urban particles (metals), ozone, smoke particles and acrolein.  A common element in the actions of these agents is the apoptosis of alveolar macrophages.  We are investigating the role of apoptosis as an early and regulatory step in the etiology of lung disease and propose that preferential apoptosis of suppressor macrophages leads to the formation of an inflammatory state in the lung.  Current research areas are to characterize the mechanism(s) of macrophage induced apoptosis by the above agents and to test the hypothesis that ratios of different macrophage populations regulate inflammation and immune activity in the lung.  This work examines surface receptors, such as scavenger receptors, for the particles; signal transduction pathways (particularly tyrosine kinases and phosphatases, as well as transcription factors such as NF-kB) and caspases in macrophage apoptosis and characterization of human alveolar macrophage subpopulations.  In addition, our work is also evaluating the role of heme oxygenases and stress proteins as antioxidants and protection against apoptosis by oxidant stress.  These studies are being examined using traditional tools in a cell biology laboratory including transgenic and knockout mice and human subjects.  The goals of the studies are to develop strategies to identify subjects at greatest risk of developing lung injury, develop new methods to prevent or halt to progress of lung inflammation and evaluate the risk of human disease from environmentally and occupationally-derived toxic agents.

Areas of expertise: Chronic Lung Diseases; Human Environmental Health; Inflammation Caused by Medical Devices; Nanomedicine; Particulates and Nanomaterials