Dr. Lowenstein's research focuses on the regulation of vascular inflammation and thrombosis. Endothelial cells respond to vascular injury by activating the exocytosis of endothelial granules, Weibel-Palade bodies, that release pro-thrombotic and pro-inflammatory mediators into the blood. Our laboratory discovered the identity of the proteins that mediate endothelial exocytosis, including members of the SNARE family and NSF. We then discovered that nitric oxide (NO) regulates vascular inflammation by chemically modifying NSF, thereby inhibiting exocytosis (Matsushita et al. Cell 2003). This discovery has profound biological significance. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell killing. Granule exocytosis is also a critical step in platelet activation. We have found that NO inhibits thrombosis in part by decreasing platelet exocytosis of alpha-granules, dense granules, and lysosomal granules (Morrell et al. Proc Natl Acad Sci U S A. 2005). Current projects now explore the mechanisms by which NO and other neurotransmitters regulate platelet activation. We have also developed novel drugs that inhibit vascular inflammation by blocking endothelial exocytosis. | 
