Molecular pathway identification

By screening commercially available small molecule inhibitor compounds and other chemical agents known to modulate specific signal transduction pathways, we have revealed roles for retinoic acid (RA) (Lipscomb et al., 2006) and Rho GTPase (Reed et al., 2009) signaling in gut morphogenesis.

Components of the Non-canonical Wnt Pathway
©Trends Genet. 2002 Sep;18(9):447-55.
credit: Dina Myers and Diane Sepich

Drug discovery

By screening novel compounds (synthesized by a collaborator, Alex Deiters), we have identified new drug-like smallmolecules that affect the cellular processes involved in gut development. Because similar processes are involved in diseases such as cancer and fibrosis, these compounds may be leads for anti-fibrotic or anti-metastatic drugs (see Dush et al., 2011).

Developmental Toxicology

Because of their rapid development, transparency, ease of use, and low cost, frog embryos are routinely employed in ecotoxicological assessments to identify potential human teratogens and developmental toxicants. By identifying the classes of chemical compounds that perturb digestive organ development in frogs, we are contributing to the assessment and identification of potential anthropogenic toxins--with additional implications for the role of environmental chemicals in global amphibian population decline (see also our work on Gut Evolution). Moreover, considering the unexplained high frequency of intestinal malrotation in the human population, such strategies may provide new insight into the role of the environment in the etiology of digestive organ birth defects.