Research InterestsOrganogenesis and human disease
Research AreaOur long-term goal is to provide insight into the molecular mechanisms responsible for the coordinated development of complex organ systems, which has relevance to human congenital birth defects, and cryptic susceptibilities to disease or syndromes. We are working on how the pancreas forms, and on how these genetic and epigenetic mechanisms control how lineage decisions are made, first in choosing the pancreas fate over stomach, liver, duodenal, and bile duct fates. We work on this problem in human tissues during the stages in which strong predisposition to type I autoimmune diabetes can emerge, and in mouse tissues where we can undertake precision genetic and other types of perturbational manipulation, as well as select specific cell types for molecular-genetic, biochemical and physical interrogation. We work on: • The principal genes that control acquisition of the pancreatic organ fate. • The “run program” that allows a surprisingly small number of progenitors in the initial pancreas anlagen to turn into a much larger organ with precisely arranged endocrine- and exocrine-functioning cells. • The production of endocrine cells of the pancreas within a dynamic epithelial niche, which we have recently redefined in several foundational publications. • How the pancreatic epithelium forms this niche and slowly becomes resolved to a simpler ductal state • How endocrine cells are progressively produced from endocrine-biased (lineage-primed) mitotic progenitors, then on to post-mitotic cells that depart the epithelium and cluster into islets of Langerhans. • Human TF genes mutated in permanent neonatal diabetes & other diseases and tissue malformation. • Cryptic epigenetic mis-programming. For example, Mnx1 deficiency allows endocrine cells to continue their normal lineage program as insulin-producing beta cells, until a specific time postnatally when receiving some form of signal that causes rewiring of their GRNs, and a sudden and complete switch into somatostatin-producing delta cells.
Current MembersWright, Christopher V (Principal Investigator/Director)
Additional InformationMolecular embryology /vertebrate embryogenesis /transcription factors/intercellular signaling
ContactInstitution: Vanderbilt University Address:
Department of Cell and Developmental Biology
Web Page: https://lab.vanderbilt.edu/wright-lab/