Oral epithelium derived dental epithelial cells go through multiple developmental stages to differentiate into ameloblasts, which are responsible for enamel formation. Enamel is the hardest mineralized tissue in our body, and the main line of defense for dental decay. Enamel cannot regenerate itself since ameloblasts commit apoptosis when teeth erupt. My research has been focusing on bioengineering functional human ameloblasts from accessible human non-dental epithelial cells, which aims to fill the gap of lack of a cell source for enamel tissue bioengineering and eventually tooth repairing. We are aiming to use transcription factors that we have identified to reprogram adult dental mesenchyme and enhance its instructive potential in driving the differentiation of recombined non-dental epithelial cells. In another parallel effort, we are using transcription regulators that are critical for enamel formation to directly transdifferentiate human non-dental epithelial cells.