The epithelial lining of the intestine allows for absorption of nutrients, electrolytes, and fluid while preventing unwanted microbes from entering the body. One cellular subtype within the epithelium, the enteroendocrine population, secretes hormones that direct digestion and absorption. Several disorders which disrupt the enteroendocrine lineage cause a congenital diarrheal disorder. Further, one of the secreted hormones, GLP-2, is a known treatment for short bowel syndrome. Using animal models, the Terry Lab investigates how the enteroendocrine lineage is specified by different transcription factors. These studies will provide a better understanding of why disruption of the enteroendocrine system causes diarrhea, identifying novel ways to treat the diarrheal illness.
Further, thanks to the generosity of patients and their families, the Terry Lab collaborates with the Ghanem Lab to maintain an Enteroid Biorepository. Enteroids are three-dimensional ‘mini-guts’ grown in culture from the epithelial cells of a single biopsy. Thus, with patient-derived tissue in culture, nutrient absorption and electrolyte secretion characteristics can be determined in a variety of disease states. For patients with congenital diarrheal disorders or short bowel syndrome, these enteroids will provide an excellent model system for future drug screening.
- Transcription Factor Specification of the Enteroendocrine Lineage
The Terry Lab has characterized the role of two transcription factors, Arx and Isl1, in lineage allocation of a subset of enteroendocrine cells. Ongoing studies are determining the direct downstream targets of these transcription factors and whether they are sufficient to restore the enteroendocrine lineage.
- Enteroid Modeling of Congenital Diarrheal Disorders
Three-dimensional enteroids (‘mini-guts’) can be grown in culture from the epithelial cells isolated from a biopsy obtained during endoscopy. The Terry Lab is currently determining the enteroid phenotype in different diarrheal disorders for further drug screening.
- Translational Research in Short Bowel Syndrome
The Terry Lab is also involved in collaborative projects investigating the gut microbiome in short bowel syndrome and the role of pancreatic enzymes in treating short bowel syndrome.