B. Mark Evers, M.D., Professor and Roberston-Poth Distinguished Chair in General Surgery
Current research interests include the evaluation of cellular mechanisms leading to the differentiation of the developing intestine and the growth of normal and neoplastic GI tissues.In addition, the developmental pattern of gene expression in the gut is also a specific area of interest using the human neurotensin gene, which is expressed in the gut in a strict spatial and temporal pattern and then re-expressed in various colon cancers.We have identified various cis-acting elements that are responsible for high-level neurotensin gene expression in the gut. Furthermore, we have found that the ras signal transduction pathway participates in this high level constitutive expression of neurotensin.We postulate that a better understanding of the developmental and age-related changes in neurotensin gene expression will provide a better understanding of the specific cellular mechanisms regulating neurotensin-induced proliferation of gut mucosa. Furthermore, we believe that the neurotensin gene will provide an important endocrine model to better delineate the complex mechanisms leading to differentiation of the gut through either a small bowel or colonic phenotype and, in addition, will provide a unique paradigm to further investigate the factors regulating the establishment and maintenance of certain cell lineage-specific patterns along the cephalocaudal axis of the gut.
Another area of active interest in the laboratory is the better understanding of the signaling pathways which contribute to intestinal cell differentiation.Our laboratory has examined, in particular, downstream effectors of the Ras signaling pathway.We have shown that the PI3-K/PTEN pathway contributes to the differentiated state in the intestine.Downstream targets of PI3-K inhibition include the homeobox gene Cdx-2 and TRAIL, a novel member of the TNF family. These studies are critical to our better understanding of normal intestinal homeostasis and may provide for novel therapeutic strategies in the treatment of gut neoplasias.
