Core Laboratory for Sputum Quality Assurance and Sputum Analysis

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Investigator: John V. Fahy, MD
Sponsor: Pennsylvania State University

Location(s): United States

Description

The research program in the Fahy laboratory aims to uncover disease mechanisms, develop disease biomarkers, and evaluate novel treatments for airway disease, especially asthma.

Our program is truly translational, encompassing clinical trials and investigations in patients and studies of disease mechanisms in cell culture and animal model systems. We have two major areas of activity:

1. In clinical studies the Fahy lab aims to provide a molecular understanding of the clinical heterogeneity of asthma. Our clinical research is enabled by methods we have optimized for application in human studies to advance knowledge about patterns of airway inflammation and remodeling and about the biophysical and biochemical characteristics of pathologic airway mucus. For example, in microarray studies of the airway epithelium we profiled the transcriptome in airway epithelial brushings from asthmatic and healthy subjects to identify molecular signatures of distinct asthma subtypes. Our studies in these areas are often done with collaborators including Prescott Woodruff’s lab and investigators at Genentech. Our clinical laboratory is also a resource for proof of concept studies of novel anti-inflammatory drugs, and we have designed and led numerous early phase studies in asthma and COPD.

2. In bench laboratory studies the Fahy lab focuses on mechanisms of epithelial cell dysfunction in asthma, including studies of airway mucus. Mucus pathology is an important cause of airway infection and pathologic mucus plug formation in airway disease. Mucin glycoproteins are a key component of airway mucus, and our lab has a specific interest in how mucin glycans participate in mechanisms of microbial adhesion and abnormal mucus rheology. We have a particular interest in fucose- and galactose-binding lectins. Together with collaborators at University College Dublin and the University of Montreal, we are investigating if inhibition of these lectins will disrupt lectin glycan interactions in airway mucins and yield novel anti-adhesion and mucolytic agents. 
Another major emphasis in our bench laboratory is the study of periostin as a novel mediator of epithelial mesenchymal communication in asthma. Periostin had been considered a matricellular protein but we have shown marked upregulation of periostin in airway epithelial cells in asthma. We have also discovered that epithelial cell-derived periostin in asthma is secreted into the sub-epithelial matrix to cause TGF-beta activation and increases in collagen gel elasticity. This is a good example of how we like to take an observation in human biospecimens and follow it up in experimental systems to improve understanding of how the airway epithelium regulates and influences events in the underlying matrix.