Hirschsprung’s Disease

Hirschsprung’s disease is a developmental disorder that affects every one in 5000 births. It is characterized as absent ganglion cells in the hind gut. The ganglion cells are necessary for gut motility and defecation. Without ganglion cells, the affected colon atrophies and the proximal bowel becomes dilated. With no gut motility, obstruction can occur, which can be life threatening.

Current research in Hirschsprung’s uses chicks as a model for the development of the enteric nervous system. By using chick/quail chimeras with antibody labeling, it is possible to track the enteric nerve development in the hind gut. Possible genes associated with Hirschsprung’s are RET (tyrosine receptor kinase used in neural signaling) and GDNF (growth factor Glial cell line-Derived Neurotrophic Factor). From what is currently known, Hirschsprung’s is incredibly heterogeneic. The chick might be a limited model to study this disease considering the difficulty in doing loss of function or gain of function transgenics.

Much more research on enteric nervous system development is needed. The only treatment for Hirschsprung’s is surgical correction by resecting the aganglic colon. Not only is this a laborious surgical procedure, but it is an uncomfortable and painful experience for the child. further research into the causes of Hirschsprung’s could develop better treatment options for this already fragile patient population.

Below: Anatomic distribution of ganglia in the intestine. Creative Commons Attribution-Share Alike 4.0 International license. Attribution: Goran tek-en

 

Current Research at Vanderbilt

Dr. Michelle Southard-Smith and her lab are looking at SOX10 expression levels in the enteric nervous system in mice to study visceral organ innervation. In these projects, the team uses mouse models to illustrate a fate map for neural crest development into the enteric nervous system and lower urinary tract.

 

Vanderbilt Digestive Disease Research Center is a collaborative funded by the NIH  to promote integrative digestive research among clinicians and researchers. Their mission is to facilitate the transfer of basic research discoveries to improvements in prevention and/or clinical care.

 

The Vanderbilt-Ingram Cancer Center SPORE in GI Cancer is a multi-disciplinary research team consisting of basic scientists and clinical investigators working together to improve the lives of those with colorectal cancer through research. Some discoveries they have made are:

• Discovery of a novel Wnt antagonist (pyrvinium) and its target (casein kinase 1a)
• Discovery of a biologically-based, prognostic gene signature for colorectal cancer
• Evidence that p120 acts as a tumor suppressor in colorectal cancer
• Development, biological validation and clinical implementation of novel molecular imaging modalities to predict early response to treatment
• Further development of a unique biorepository of colorectal adenomas, as well as matched normal rectal mucosa and bodily fluids (serum and urine)

More information on their current projects can be found on their website.