Heuckeroth Laboratory

The bowel is nearly 30 feet long in adults and every region must respond to local stimuli (e.g., nutrients and stretching) to optimally manage complex and unpredictable intake without conscious thought. Fortunately, the bowel has its own elaborate nervous system called the enteric nervous system (ENS) that responds to sensory stimuli and controls most aspects of bowel function.

The ENS has about 500 million neurons and 2-5x as many glial cells. There are an estimated 20 neuron types that have distinct functions, neurotransmitters, morphology, and receptors. These ENS cells coordinate contraction and relaxation of the bowel, regulate blood flow, and influence epithelial function in response to local sensory stimuli. To perform these tasks, the ENS interacts closely with many other cell types including smooth muscle, pacemaker cells (interstitial cells of Cajal), enteroendocrine and other epithelial cells, muscularis macrophages and cells of the immune system, as well as with extrinsic innervation. When the ENS does not form properly or is not working well, profound bowel dysfunction may occur causing diseases like Hirschsprung disease, chronic intestinal pseudo-obstruction syndrome, achalasia, and gastroparesis.

The goal of the Heuckeroth Lab is to define molecular and cellular mechanisms that are needed for normal bowel function. The team aims to understand genetic and non-genetic factors that cause disease to enhance the ability to make diagnoses, develop new treatment strategies, and find ways of preventing bowel motility disorders from occurring in the first place.

The lab uses the most advanced approaches including model systems, sequencing, bioinformatics, stem cell biology, imaging, and regenerative medicine strategies. Current studies focus on ENS and smooth muscle biology, with many collaborative projects that span disciplines of medicine and biology.

Project Highlights

Current projects in the Heuckeroth Lab involve the following:

• Enteric nervous system development and function
• Smooth muscle development and function
• Genetics of bowel motility disorders
• Gene-environment interactions
• Stem cell biology
• Regenerative medicine
• Transcriptional regulation of cell fate
• MicroRNA in the ENS
• Retinoic acid and the ENS
• Chronic intestinal pseudo-obstruction and Hirschsprung disease
• Three dimensional imaging ENS anatomy
• Gut microbiome, enterocolitis and development