SUMMARY
As a researcher, Kristen M. Smith-Edwards, Ph.D., is focused on the neural pathways of the gut-brain axis that regulate colon function in healthy and diseased states. The gut has its own intrinsic nervous system, called the enteric nervous system, which is capable of executing gastrointestinal (GI) functions. However, to maintain homeostasis and overall health, the brain and gut communicate with one another by sending signals via extrinsic sensory and autonomic nerve pathways.
Dr. Smith-Edwards and her research team utilize approaches in preclinical models to understand how enteric, autonomic and sensory neurons, as well as non-neuronal target cells in the bowel, work together to mediate motility, inflammation and abdominal pain. Dr. Smith-Edwards and her research team's long-term goals are to determine the neural mechanisms underlying GI disease and develop new therapeutic strategies that modulate neural activity to treat GI dysfunction.
Focus areas
- Defining and modeling the cellular interactions that produce rhythmic colon motility. Continuous colon motility is critical for overall health and results from activity in the enteric nervous system, interstitial cells of Cajal and smooth muscle. Although these cell types have been individually studied in detail, how they interact to coordinate motility across the length of the colon is not well understood. Dr. Smith Edwards' lab uses optogenetic- and calcium-imaging approaches to manipulate and record activity in each of these cell types. At the same time, her team monitors the changes in motor patterns to define the cellular interactions responsible for colon motility. Dr. Smith-Edwards and her research team's goal is to build a computational model that will help predict the cellular mechanisms of dysfunction in GI disease and guide optimization of electrical stimulation devices to normalize motility.
- Neuroplastic changes in the gut-brain axis that contribute to pain and dysmotility. Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are GI diseases that commonly present with dysmotility — constipation or diarrhea — pain and autonomic dysfunction. The presence of these conditions suggest that extrinsic nerve pathways of the gut-brain axis are involved in disease pathology. Dr. Smith-Edwards has identified unique sensory and autonomic motor functions for each of the three pathways that travel between the brain and colon. Researchers in Dr. Smith-Edwards' lab are now using preclinical models of IBD and IBS to determine the changes in each pathway that contribute to pain and dysmotility.
- Mechanisms underlying long-term bowel dysfunction in Hirschsprung disease. Hirschsprung disease (HD) is a congenital defect resulting in the lack of an enteric nervous system in the distal bowel. Although HD is treated surgically by removing the affected portion of bowel that is missing the enteric nervous system, HD patients continue to suffer from bowel complications including dysmotility, enterocolitis and inflammation. Dr. Smith-Edwards generated an HD mouse model and identified significant defects in enteric nervous system activity in the proximal bowel that likely contribute to bowel dysfunction following surgery. Her lab collaborates with pediatric surgeons, gastroenterologists and pathologists at Mayo Clinic to optimize surgical protocols, design novel diagnostic approaches and develop new treatments to improve the long-term outcomes in HD patients.
Significance to patient care
Dysfunction in the gut-brain axis has been linked to a wide variety of GI and non-GI related diseases that affect millions worldwide. The most common GI symptoms, pain and dysmotility, are notoriously difficult to treat without unwanted side effects. Dr. Smith-Edwards and her research team are diligently working to determine the neural mechanisms underlying GI dysfunction. They hope to leverage the unique functions of enteric, sensory and autonomic nerve pathways to develop new treatments that use neuromodulation to reduce suffering and improve long-term outcomes in patients.