Paul McCray, MD, is a pediatric pulmonologist with a long-standing interest in airway epithelial cell biology, innate immunity, and the applications of gene transfer for lung diseases.
Pulmonary Host Defense
Despite the intimate contact between the lung and the external environment that occurs with each breath, the intrapulmonary airways are normally free of infection and inflammation. A well-orchestrated mucosal immune system contributes to this remarkable state of affairs. We are broadly interested in host-pathogen interactions, defense mechanisms, and epithelial responses to bacteria and viruses. The lab has a major interest in the pathogenesis and treatment of cystic fibrosis. Additional studies are investigating interactions between airway epithelia and specific pathogens (RSV, influenza, PIV, SARS and MERS coronaviruses, others).
Studies of the anti-microbial properties (anti-bacterial, anti-viral) of airway surface liquid stimulated an interest in the functional properties of host defense proteins and peptides secreted by epithelia. Antimicrobial proteins and peptides play important roles in the innate and adaptive mucosal immune responses of the lung and defects in their function may contribute to the pathogenesis of lung infections in cystic fibrosis. We are using large-scale gene expression and genomics approaches to study epithelial cell mRNA and microRNA gene networks and programs underlying host defense responses. We wish to apply knowledge from these studies towards new molecular therapies.
Genetic therapies for the treatment of inherited diseases
The laboratory is performing a variety of gene transfer studies using lentiviral and transposon vectors. We have developed novel FIV lentiviral vector pseudotypes that target receptors on the apical surface of airway epithelia. We are also exploring other nucleic acid based interventions including RNA interference and gene editing for therapeutic purposes. In addition. we are investigating genomics approaches such as the connectivity map to identify small molecules to rescue CFTR function. A long-term goal is to develop vector systems with that can be successfully used in children to treat or prevent CF lung disease by gene addition or gene repair.