Project R-16450

microRNA-regulation of the neurogenic potential of enteric glia (Research)

The enteric nervous system (ENS), the little brain in our gastrointestinal tract that regulates digestive function, is composed of meticulously wired networks of enteric neurons and glial cells. Disorders involving compromised ENS integrity and concomitant gut dysmotility are significant contributors to the global health burden. However, the existing treatment options for severe ENS diseases focus on managing symptoms or involve surgical removal of the affected gut segments, but do not address the absence or loss of ENS cells. Enteric glia, surpassing their role as passive bystanders in ENS function, possess the intrinsic capacity to generate new neurons. Our preliminary data suggests that enteric glia are equipped with a unique microRNA expression profile instrumental to their neurogenic potential. microRNAs are small non-coding RNAs that regulate gene expression networks, strongly impacting cellular differentiation. In this project, we will determine whether microRNA modulation can be used to reprogram enteric glia, engaging their neurogenic potential with the goal of restoring ENS activity. The combination of a variety of model systems and sophisticated molecular tools empower the studies to identify specific microRNAs, which will be targeted to convert enteric glia to neurons, offering a new therapeutic avenue for gut motility diseases.

01 January 2026 - 31 December 2029