Washington University in St. Louis (WU)
Our overall interest is to delineate molecular signals that regulate organogenesis and determine their role in injury and regeneration. We use glial cell line-derived neurotrophic factor (GDNF) family ligands-Ret receptor tyrosine kinase signaling system as a paradigm. This signaling system is associated with a number of human diseases including developmental abnormalities, neurodegenerative diseases and cancer syndromes. Using genetically defined Ret signaling mutants we have identified molecular basis for signaling specificity in the development of urogenital system and currently extending these to peripheral and central nervous system. Our future goals are to understand the role of Ret signaling in self-renewal after injury, determine roles and mechanisms of GFLs in therapy, use bioinformatics and genomic approaches to identify downstream signaling molecules that mediate Ret’s pathological effects and translate these discoveries into humans.