The research focus of my lab focuses on the molecular mechanisms underlying normal and pre-neoplastic epithelial cell growth in the luminal gastrointestinal tract. My recent studies involve the use of animal and cell culture models to dissect the pathways through which chronic inflammatory processes, generally from bacterial colonization, leads to mucosal alterations of the luminal GI tract sets the stage for neoplastic transformation (pre-neoplasia). Ongoing projects in my laboratory include the role of sonic hedgehog in gastric homeostasis, e.g., acid secretion and chronic gastritis leading to metaplasia/dysplasia; the role of the nuclear protein menin in the genesis of neuroendocrine tumors, e.g., gastrinomas, carcinoids, and the role of the Krüppel-like transcription factor ZBP-89 (ZNF148) in mucosal restitution from infection to neoplastic transformation. We have used mouse models to dissect the role of Hedgehog signaling in the stomach during chronic inflammation. Over the past 18 years, my lab has established a major role for Hedgehog signaling in normal gastric physiology and during gastric preneoplasia. My initial studies demonstrated that parietal cells and therefore acid secretion requires sonic hedgehog signaling. More recently, studies from my lab have revealed that myeloid-derived suppressor cells (MDSCs) require Hedgehog signaling to create a permissive environment that supports the development of gastric metaplasia, a mucosal lesion preceding cancer.
