Interstitial Cells of Cajal

Although motility disorders affect millions of people, the underlying pathophysiology of these disorders has long been unclear. Dr. Farrugia's research team has studied the cellular basis of motility diseases for more than 20 years. In 2000, the lab published the first study showing that loss of ICC is the main defect in slow transit constipation. Since then, the team has shown that ICC defects are present in intestinal pseudo-obstruction and gastroparesis.

Coordinated electrical activity in the gastrointestinal tract requires the interaction of several cell types, including nerves, interstitial cells of Cajal and smooth muscle cells. Interstitial cells of Cajal generate the electrical slow wave that drives regular smooth muscle contractility.

Over a series of more than 20 manuscripts, the Cellular and Molecular Physiology of Gastrointestinal Disorders Lab has combined electron microscopy and light microscopy to show that more than 95% of people with gastroparesis have abnormalities in interstitial cells of Cajal, and that when the deficit in interstitial cells of Cajal is corrected in animal models, normal gastric emptying is restored. The lab is now focused on discovering novel targets and therapies to treat gastroparesis.

The lab has also identified how defects in ion channels expressed in interstitial cells of Cajal, such as ANO1 and NaV1.5, lead to abnormal function and disease and is investigating the molecular mechanisms for pacemaker generation in some but not all subtypes of interstitial cells of Cajal. Read more about the Cellular and Molecular Physiology of Gastrointestinal Disorders Lab's research on mechanosensitive ion channels.