Paul McCray, MD, is a pediatric pulmonologist with a long-standing interests in airway innate immunity, epithelial cell biology, and the applications of gene therapy for lung diseases.
Genetic therapies for the treatment of inherited diseases
The laboratory is performing studies using lentiviral and AAV vectors. Our major disease focus is cystic fibrosis. We have developed novel lentiviral vector pseudotypes that target receptors on the apical surface of airway epithelia. We are also exploring gene editing and base editing to correct mutations in airway progenitor cell types. 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.
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 interested in host-pathogen interactions, defense mechanisms, and epithelial responses to bacteria and viruses. We are investigating how respiratory viral infections may contribute to the genesis of cystic fibrosis lung disease. Additional studies are investigating interactions between airway epithelia and specific pathogens (RSV, influenza, PIV, SARS, MERS, SARS-2 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.