Dr. Bowser’s Research

Targeting Epithelial Regeneration for Perioperative Organ Protection.

Bacteria movement into the blood and excessive inflammation due to intestinal injury is a significant cause of multiple organ failure (MOF) in surgical and critically ill patients. Anesthesiologists and intensivists commonly encounter patients with MOF, which is a devastating concern worldwide as it is the cause of more than 50% of deaths in the perioperative setting. Clinical trials targeting intestinal inflammation for reducing MOF have had very little success. Uncovering new molecular mechanisms and druggable targets for intestinal injury and thereby MOF are greatly needed. A key to this may be preventing intestinal injury and subsequent bacteria translocation by promoting the regeneration (increase cell division) of the epithelial cells. Current therapy approaches for epithelial regeneration are limited to medically extensive procedures, which have a high incidence of serious complications. No drugs are known to be able to increase epithelial regeneration. Our previous studies have shown adenosine signaling protects intestinal epithelial cells during intestinal inflammation. Our exciting preliminary data indicates that adenosine signaling promotes epithelial cells to divide efficiently. Increasing the efficiency of cell division may increase epithelial regeneration and thereby promote intestinal healing, which would prevent MOF. We proposed to: 1. Study the mechanism of adenosine signaling in promoting efficient intestinal epithelial cell division; 2. Define adenosine signaling as a therapeutic target and druggable approach for increasing epithelial regeneration and thereby healing intestinal injury. Adenosine signaling is an attractive therapeutic target, as many drugs targeting this pathway are already in clinical trials for other diseases/health conditions. Thus, if our studies are successful, there is a real opportunity to move this work towards clinical studies for MOF.