Keith Tucker Wilson, MD
Dr. Wilson has conducted highly original and fundamental research related to gastrointestinal mucosal immunology and inflammation. In his early work he identified that nitric oxide (NO) induces colonic secretion, which impacted on the field of intestinal electrolyte transport. He then focused on inducible nitric oxide (NO) synthase (iNOS) and cyclooxgenase (COX)-2 in mucosal inflammation, including pioneering work in both Helicobacter pylori infection and Barrett’s esophagus. To better understand the complex role of iNOS-derived NO in mucosal inflammation, Dr. Wilson investigated the role of arginase, which competes with iNOS for the same substrate, L-arginine. This work resulted in 3 novel findings: 1) In colitis, arginase I is upregulated and has a beneficial role by generating substrate for synthesis of polyamines involved in cell restitution and inhibition of inflammatory responses. 2) H. pylori arginase competes with host iNOS and prevents NO-mediated bacterial killing. 3) In H. pylori infection, arginase II is upregulated and results in macrophage apoptosis by generation of polyamines. Dr. Wilson then discovered that spermine oxidase (polyamine oxidase 1), which metabolizes spermine, is induced by H. pylori and causes apoptosis of macrophages and epithelial cells by generation of hydrogen peroxide and this oxidative stress also results in DNA damage in gastric epithelial cells. He has also demonstrated that spermine inhibits iNOS and NO-mediated bacterial killing via a block in iNOS translation. Dr. Wilson has provided important novel insights into the immune dysregulation associated with H. pylori infection that have major implications for mucosal immunology and inflammation-associated carcinogenesis.