My laboratory has found, both in vivo and in vitro, that lung epithelial cells are sufficient to kill a wide variety of respiratory pathogens. By stimulating the epithelium with combinations of pathogen-associated molecular patterns (primarily Toll-like receptor ligands), we induce intrapulmonary killing of pathogens, and demonstrate striking survival improvements despite challenges with Gram-positive, Gram-negative, viral, fungal, and even bioterror pathogens.
Graduate students in my laboratory focus on projects related to the mechanisms underlying the inducibility of microbial resistance in the lung epithelium.
Potential graduate student projects may include:
- Determination of the necessary and sufficient epithelial cell populations for induction of resistance
- Dissection of the signaling pathways that promote synergistic protection
- Identification of the epithelium-derived effector molecules that promote pathogen killing, such as antimicrobial peptides and reactive oxygen intermediates.
These objectives are primarily investigated in vivo using knockout and transgenic mice to manipulate the genes of interest, and in vitro using epithelial cell culture techniques.