Robert O. Heuckeroth, MD, PhD
Our research is focused on molecular mechanisms of development with a special interest in the development of the enteric nervous system (ENS). The ENS is a complex network of neurons and glial cells within the bowel wall that controls most aspects of intestinal function. To perform these tasks there are estimated to be 500 million neurons in 20 functional classes in humans. All of these cells, and their supporting glia arise from a population of neural crest-derived precursors that migrate through the bowel, proliferate profusely and then differentiate and extend neuronal projections to form a functional interacting network. Defects in ENS development cause Hirschsprung disease and other intestinal motility disorders. Establishing the enteric nervous system requires the coordinated action of many cell surface, intracellular and extracellular mediators. Over the past few years we have described gene expression patterns in the bowel for hundreds of genes and identified new functional roles for more than a dozen proteins in ENS development. Ongoing work in our laboratory is directed toward the identification and functional characterization of novel genetic and non-genetic mediators of enteric nervous system development with the goal of identifying new ways to treat or prevent intestinal motility disorders.