My research focuses on analyses of gastrointestinal proliferation, differentiation, and malignant transformation. Recently, my laboratory has concentrated on KLF4 and KLF5, two related Krüppel-like factor (KLF) family members highly expressed in the gastrointestinal epithelia. KLF4 and KLF5 are important regulators of cellular proliferation and differentiation both in vitro and in vivo. Numerous studies implicate these factors in carcinogenesis in a number of tissues and cell types. Using tissue-specific gene ablation and transgenic approaches, we have generated a number of mouse models to investigate the function of Klf4 and Klf5 in development and gastrointestinal epithelial homeostasis in vivo. These mouse models are complemented by novel in vitro model systems, using primary esophageal cells in two-dimensional culture and three-dimensional organotypic culture. These experiments allow us to dissect the molecular mechanisms regulating gastrointestinal epithelial homeostasis, including the role of epithelial-mesenchymal interactions. Using these in vitro and in vivo models, we are examining the specific factors which control the balance between proliferation and differentiation in gastrointestinal epithelia and the elements which disrupt this balance during mucosal injury and carcinogenesis.