Throughout my research training and career I have been focused on understanding the cellular and molecular mechanisms that drive intestinal organogenesis and maintenance. Specifically, I am deciphering the signaling network between the epithelium and mesenchyme that directs villus formation and interactions between the intestinal stem cells and their niche that maintain the villi. My work has contributed several key advances in techniques that have greatly improved analysis of fetal intestines including the development of a whole organ culture system that can be used for live imaging, and improved methods for preparing tissue for high resolution confocal imaging and three-dimensional reconstruction towards visualization of whole intestinal structures. Using this culture system, along with genetic mouse models that alter the signaling networks, I have identified and characterized a Hedgehog signaling dependent aggregation of mesenchymal cells (clusters) that form just prior to villus emergence and act as a signaling center to direct and pattern villus morphogenesis. Downstream from Hedgehog, Bmp signaling in the mesenchymal clusters feeds back to the epithelium and to the developing vasculature underlying the epithelium to promote villus development. My current studies examine the role of vasculature in patterning mesenchymal clusters and villi. Combining information gleaned from genetic mouse models where fetal villus vascular development is altered with information from host supplied villus vasculature vasculature in kidney capsule transplanted human intestinal organoids is providing important insight into mechanisms that drive villus emergence. In addition, I have developed human intestinal stem cell lines and protocols for bioluminescent imaging to track the growth of transplanted human intestinal organoids over time and following injury. The ultimate goal of my work is to apply the mechanisms controlling development and maintenance of the villi towards engineering functional intestinal tissue that could be transplanted or stimulating the growth of villi and intestines in patients with short bowel.