Mawe Lab Research

Neural regulation of the digestive tract - understanding changes in enteric neural circuits that contribute to altered gut function in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS)

Neurons in the wall of the intestines control how the gut reacts to an ingested meal, and they regulate the processes of digestion, nutrient absorption, and waste elimination. In states of inflammation, such as Crohn’s disease or ulcerative colitis, various features of gut function, including motility, secretion and sensitivity are altered. As nerve cells of the bowel regulate all of these functions, it is likely that changes in these neurons cause the symptoms that lead to so much suffering in these individuals. Discoveries in gut neurobiology over the past two decades have provided us with a solid understanding of the components that make up gut reflex circuits, and how these neurons function under normal physiological conditions. We are now examining what changes occur in various parts of the reflex circuits and the mechanisms responsible for these changes.

Determining how disruptions in gallbladder muscle function occur, and how they contribute to the development of gallstone disease

Gallbladder disease is one of the most common digestive disorders, and hallmark properties include decreased contractility, inflammation, and gallstone formation. Recent reports suggest that decreased gallbladder motility is caused by elevated cholesterol and hydrophobic salts in the bile, and that ensuing inflammation and impairments in gallbladder emptying lead to stone formation. Furthermore, mounting evidence suggests that hydrophilic bile salts may have therapeutic potential by restoring gallbladder smooth muscle contractility and reducing gallstone development and inflammation. Nevertheless, the interrelationships between decreased contractility, inflammation, and gallstone formation are not understood, and this reflects our lack of understanding of the cellular events that lead to gallbladder muscle dysfunction in gallstone disease. The objectives of our ongoing research are to: (1) elucidate the cellular and ionic mechanisms by which gallbladder smooth muscle contractility is disrupted in gallstone disease; (2) determine the role of inflammation in smooth muscle dysfunction and associated biliary stasis in gallstone disease; and (3) explore the utility and mechanisms of hydrophilic bile salts in the protection of gallbladder function by preventing or reversing these disruptions.

Serotonin signaling in the mucosa layer of the gastrointestinal tract

We typically think of serotonin as a neurotransmitter in the brain, but most of the body’s serotonin is actually located in the gastrointestinal tract, and this is where serotonin was initially discovered. Within the wall of the gut, serotonin is used as a transmitter by interneurons, but the real mother lode of serotonin is synthesized by specialized cells in the inner lining of the intestine, called enterochromaffin (EC) cells. Serotonin released by EC cells activates receptors on nearby nerve fibers to activate reflexes involved in fluid secretion into the lumen and coordinated muscle responses that propel ingested food and fluids along the intestines. Serotonin signaling in the intestine is stopped via reabsorption (reuptake) by a protein called the serotonin transporter (SERT). This is the same serotonin transporter that stops 5-HT signaling at synapses in the central nervous system. It also is the molecule whose function is inhibited by serotonin selective reuptake inhibitors (SSRIs), which are commonly prescribed for the treatment of depression and anxiety disorders. In the gut, SERT is located on essentially all of the cells that line the intestines. Therefore, it is as though the gut has a huge sponge responsible for regulating levels of 5-HT, and this is further evidence of the importance of 5-HT signaling for gut function. Studies conducted in our laboratory and others have demonstrated that various aspects of mucosal serotonin signaling are altered in humans with inflammatory bowel disease or irritable bowel syndrome, as well as animal models of intestinal inflammation. Current studies in our laboratory are directed towards understanding how these changes occur and whether they contribute to altered gut function and sensation.


Lab Personnel

Mawe Lab August 2012


Jane Roberts, Cameron Hecht, Stephanie Spohn, Amanda Bolgioni, Dr. Gary Mawe, Brigitte Lavoie.

Mawe Lab Summer 2011


(L to R) Bernhard Nausch, André-Denis Wright, Stephanie Spohn, Gary Mawe, Jill Hoffman, Hannah Foote, and Brigitte Lavoie.

Mawe Lab Winter 2010


(L to R) Brigitte Lavoie, Jane Roberts, Gary Mawe, Jill Hoffman, Elice Brooks, and Bernhard Nausch.

Mawe Lab Summer 2010