The proinflammatory effects of inhaled bacterial endotoxin:
Dr. Hasday showed that the bronchoalveolar compartment of the lung is converted from an endotoxin-insensitive to an endotoxin-sensitive environment by the leak of the endotoxin accessory molecule, LPS-Binding Protein (LBP) from the circulation.
Dr. Hasday also showed that cigarette smoke contains large amounts of biologically active endotoxin, representing a potential link between COPD and smoking and other environmental lung diseases attributable to inhaled endotoxin.
Dr. Fenton is studying the contribution of LBP to asthma using a mouse model of asthma and LBP knock-out mice. Drs. Hasday and Vogel are studying the molecular mechanism of macrophage dsyfunction in smokers, focusing on the biochemical pathways leading to endotoxin tolerance in these cells.
The roles of cytokine and lipid mediators:
Dr. Hasday (in collaboration with Dr. Eugene Bleecker) has analyzed the effects of smoking and asthma on cytokines and leukotrienes in the airways.
Dr. Hasday has shown that only half of the asthmatic subjects studied generate leukotrienes after segmental allergen challenge and responsiveness to leukotriene modifying drugs was limited to those subjects. This finding offered a biologic basis for the general perception that the leukotriene modifying drugs were effective in only half the asthmatic population.
This page was last updated: July 10, 2013