The innate immune system plays a critical role in protecting a host against invading pathogens. Well-controlled responses promote resolution of the infection while uncontrolled responses lead to toxic manifestations of systemic inflammatory response syndrome, reported to cause 100,000 deaths annually in the US. Macrophages, a major component of innate immune system, can respond by recognizing, signaling the presence of and eliminating infectious pathogens.

My research goal is to understand the mechanisms involved in the regulation of macrophage activation. Analysis of the response of macrophages to LPS led to the discovery of LPS-mimetic actions of taxol and the identification of heat shock protein 90 (Hsp 90) as a shared cellular target of taxol and LPS. Comparison of genes that are differentially expressed between LPS responder and non-responder macrophages led to the identification of secretory leukocyte protease inhibitor (SLPI) as an LPS-inducible macrophage product with LPS-antagonistic activity. Examination of SLPI's anti-inflammatory actions led to the discovery that SLPI/elastase can serve as a biological switch via proepithelin/epithelin conversion to control host defense and wound repair. We are currently continuing our studies on the molecular events involved in macrophage activation by LPS and deactivation by SLPI.