The gene responsible for causing the human disease multiple endocrine neoplasia type 1 (MEN1), menin, is being investigated. Although a genetic link between this gene and MEN1 has been well established, the biochemical role of menin and its relevant signaling pathway remain unknown. This project aims to establish a role for menin in a cell fate and pancreatic islet cell growth and to elucidate the molecular mechanism underlying this role. We hypothesize that menin affects cellular proliferation by regulating the expression of genes associated with the cell cycle. Menin function will be studied using an inducible tissue specific system that ablates the menin gene in vivo. Firstly, the effects of inducible menin loss will be examined on pancreatic function and a cell fate. Secondly, the implicated molecular pathways underlying menin signaling will be determined by analyzing changes in gene expression following inducible menin loss. If we are successful in both defining a role for menin in a cell proliferation and implicating a signaling pathway, we can extend our findings to in vitro systems and other in vivo models that would allow further characterization of menin biochemistry and gene function. This work also has therapeutic implications for treating neuroendocrine cancers as well as diabetes.
