Pediatric surgeon Bradley Segura

Surgery
Medical School
Twin Cities
Project Title: 
The Role of the Enteric Nervous System in Pediatric Intestinal Diseases

These researchers seek to examine the specific role of the sphingosine-1-phosphate receptor modulator (S1PR), FTY720, on enteric glial cells (EGCs) and intestinal epithelial cells (IECs) in the control of epithelial barrier integrity and intestinal inflammation. EGCs represent a critical component of the enteric nervous system (ENS) where they outnumber enteric neurons by 4-fold in mice and 6-fold in humans. Previously it was thought that the function of EGCs was to solely support neurons, but emerging studies demonstrate that they are indeed active members of ENS involved in immunity, inflammation, intestinal motility, and they even contribute to neurogenesis during injury. IECs play a pivotal role in blocking the entry of harmful pathogens into the gastrointestinal tract. They function as a first line safeguard by maintaining the epithelial barrier integrity thus preventing bacterial translocation and gut inflammation. Recently a sphingosine-1-phosphate receptor (S1PR) modulator, ozanimod received FDA approval to treat patients with colitis. It is widely known that S1PR modulators block the egress of lymphocytes from lymphoid tissues, therefore reducing the circulating lymphocytes and preventing inflammation at the affected sites. However, presence of S1PR receptors in other cells such as enteric glia within the ENS and intestinal epithelial cells themselves suggests that they may also be affected when exposed to S1PR modulation and these cells might also contribute to reducing the severity of intestinal disease. There is limited knowledge of the S1PR modulator’s impact on enteric glia or epithelial cells and whether they can contribute to reducing intestinal inflammation through this receptor modulator. For the effective treatment for colitis and other forms of intestinal inflammation in children and adults alike, it is imperative to understand the underlying signaling pathways and the exact mechanisms by which this drug targets the GI tract to reduce disease symptoms and better manage our patients. Based on our preliminary data and relevant work in the CNS, these researchers believe that a relationship exists between S1P signaling and inflammation within the ENS. Their long term goal is to understand the role of the ENS in intestinal disease and to characterize its potential for preventive and therapeutic purposes. 

Project Investigators

Pediatric surgeon Bradley Segura
 
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