Pneumonia is the leading cause of infectious disease-related deaths worldwide, with treatment options limited to antibiotics and supportive care. Given the rise in antibiotic resistance and the varied etiology (virus, bacteria, fungi) of pneumonia-causing microorganisms, there is a critical need to develop host-targeted therapeutics. As such, the main focus of our laboratory is to discover host factors that contribute to immune defense (eradication of the pathogen) and tissue resilience or recovery (injury prevention and repair), which may contribute to pneumonia susceptibility and severity. To this end, we focus on the following:

1. Scavenger receptor expression and regulation during lung infection: Scavenger receptors (SRs) are a varied group of receptors contributing to the host response to infection. Recently, we showed that one of these receptors (LOX-1) prevents inflammation and promotes tissue recovery following lung infection in mice. This is in direct contrast to its role during vascular inflammation, where it exacerbates atherosclerosis. The precise mechanism of LOX-1’s uniquely protective role in the lungs is currently unknown but likely depends on the regulation of resident (macrophage) and recruited (neutrophil) immune cells. Therefore, LOX-1 signaling, ligand interactions, and impacts on immunometabolism during acute and long-term protection will be one target of our studies. Numerous other SRs (e.g., CD68, CXCL16, CD163) are also expressed in lung cells with unknown functions. As such, their cell-type-specific roles during lung infection is another focus of our lab.

2. Lipid metabolism: The lung is a uniquely lipid-rich environment, including fatty acids, phospholipids, sphingolipids, and lipoproteins, some of which (pulmonary surfactant) reduce the surface tension in the lung, allowing for proper gas exchange. However, lipids are also biologically active as signaling molecules and fuel metabolic pathways (e.g. fatty acid oxidation) with known immunoregulatory function. Whether and how many of these lipid species influence response to lung infection is unknown. Importantly, how these vary with infection type, severity, and associated co-morbidities may lend insight into inter-individual susceptibility to lung infection.