Protooncogenes-Signaling in Development and Neoplasia

All cells must communicate with their environment. They do so by recognizing extracellular signaling molecules that interact with cellular receptors to elicit a meaningful intracellular response. Transmembrane signaling by the receptor tyrosine kinases form the conceptual basis for this collaborative program. The individual laboratory components within this program interact to address basic issues in transmembrane signaling. What are the nature of the extracellular signaling molecules? How does the association of these molecules with specific surface receptors transmit a structural change across the membrane transducing the energy of ligand binding into meaningful intracellular events? How are the changes in intracellular domains of the receptor recognized by downstream signaling components to alter the growth, differentiation and migration of individual cells or cell populations and finally, how do perturbations in this signaling process result in the malignant phenotype? These conceptually related questions are approached from different directions by the individual component laboratories. Stephen Goff continues to examine the function of the Abelson tyrosine kinase during normal development as well as the transforming activity of activating forms of Abl. Frank Costantini's efforts have focused on an understanding of the function of the RET receptor tyrosine kinase in the development of the enteric nervous system and the nature of the mutations in RET that lead to a variety of human cancers. Tom Jessell's and Richard Axel's laboratories study signaling in the nervous system by molecules that define neural identity and dictate the precision of axon targeting, but in other cellular contexts are protooncogenes.