Molecular Blueprints of Organogenesis

Our highly collaborative faculty continue to discover of how gene regulatory networks orchestrate organ formation and how disruptions to these genetic programs can result in disease. For example using a combination of fruit fly genetics, quantitative biochemistry and mathematical modeling the Gebelein and Kopan labs uncovered an unexpected relationship between DNA enhancers that govern gene expression and Notch signaling metabolism; a pathway involved in many different aspects of development, homeostasis and disease. The Wells and Gebelein labs uncovered how some mutations in the Notch target gene NEUROG3 can result in pediatric diabetes while other mutations are likely to cause congenital malabsorptive diarrhea in patients, by regulating different gene programs in different tissues. The Hegde lab showed that the protein phosphatase EYA3, conserved from Drosophila to humans, is a novel therapeutic target for pulmonary hypertension, where it modulates pathological vascular remodeling. The Zorn lab used frog and mouse embryos to discover the cellular mechanics controlling trachea and esophagus formation during fetal development and showed how mutations in patients are likely to result in congenital birth defects such as esophageal atresia. The state of the art core facilities managed by the Division of Developmental Biology faculty including the Confocal Imaging Core, Transgenic Animal and Gene Editing Core, the Pluripotent Stem Cell Facility and the single cell gene expression core enables all of this cutting edge research.

Making Organs in the lab

This research in animal models provides a blueprint for organogenesis that our investigators use generate human organoid tissue in the lab providing unprecedented platforms to study human biology and one day tissue for transplantation. In a series of collaborative studies led by Takanori Takebe, MD, labs from the Divisions of Developmental Biology, Gastroenterology, Hepatology and Nutrition and the Center for Stem Cell and Organoid Medicine (CuSTOM) generated the world’s first multi-organ system in vitro consisting of liver-pancreas-gallbladder. Using this and other novel human organoids the teams used patient-mutations in pluripotent stem cells to study the basis congenital endocrine defects, biliary atresia and steatohepatitis.