Clinical Research Agenda

The enteric nervous system develops from neural crest derived cells that migrate through fetal bowel to form a complex and beautiful network of interconnected neurons and glia

Sometimes the gut just doesn't work right.  We want to understand why this occurs and find new ways to make the gut work better. We also want to find new ways to prevent problems from occurring in the first place

The gut (also called "the bowel" or "the intestine") performs a complex task converting what we eat and drink into readily absorbed nutrients and permitting us to eliminate components of our food that are not needed.  Fortunately for most people this works well requiring no conscious thought once the food is swallowed, at least until the food reaches the far end of the bowel.  This is because the bowel has it's own nervous system called the enteric nervous system (ENS) that control's bowel activity.  The ENS not only controls patterns of bowel contraction and relaxation, but also can "sense" what is happening in the bowel to determine the appropriate response.  In addition the ENS influences the cells that line the bowel (epithelial cells) and the ENS controls intestinal blood flow.  To perform these tasks, the human ENS has about as many neurons as in the spinal cord and at least 20 different types of neuron.  

In addition to the ENS, normal bowel motility requires working smooth muscle cells, intestinal pacemaker cells (called the Interstitial Cells of Cajal), and signals from epithelial cells.  These structures are in turn influenced by sympathetic and parasympathetic neurons outside the bowel, hormonal signals, gut bacteria and the food consumed. 

Because the mechanisms that control bowel motility are complicated, many different problems can cause abnormal bowel motility.  One major goal for our lab is to determine the precise problem causing bowel motility problems in seriously ill children.  We believe that this is a first necessary step to develop new treatments or cures.

Bowel Motility Disorders:

When bowel motility is abnormal, symptoms may include vomiting, bloating, abdominal pain, constipation or diarrhea.  Serious bowel motility problems can make it impossible to eat or to survive without nutrition through an intravenous (IV) line.  Problems may occur at any age and symptoms vary depending on the region of the bowel that is working poorly and the exact nature of the problem.  For some children the cells and structures required for normal motility never formed properly in the first place as the baby was developing (e.g., before birth).  These problems are considered to be "birth defects" and many will have genetic causes and perhaps non-genetic causes.  In other children and adults, the cells and structures required for normal motility work well at birth and then are damaged or degenerate.

Looking Toward Future Breakthroughs:

Over the past twenty years, our group and other investigators have learned a lot about what causes intestinal motility disorders.  This gives us great hope that new approaches to diagnosis, treatment, prevention and cure can be developed to improve the lives of people with abnormal intestinal motility.  Unfortunately, we still have a lot to learn, and we need many more treatment options.  We will be working closely with the clinical team at the Suzi and Scott Lustgarten Center for GI Motility at The Children's Hospital of Philadelphia to find ways to help children who are seriously ill because their gut does not work well.  Our work will combine cutting-edge basic research with the best of modern medicine.  You can learn about our Current Projects here including human research studies.