Kerry Kornfeld, M.D., Ph.D.

DEPARTMENT OF Developmental Biology
Keywords: development, aging, cell fate, signal transduction, cancer, Caenorhabditis elegans

Our research addresses two areas—cell fate specification during development and aging. Beautiful and intricate patterns of differentiated cells emerge during development. To investigate this process, we combine genetic analysis of C. elegans with biochemical analysis of homologous vertebrate proteins. Because developmental pathways have been extensively conserved, we can exploit the advantages of both systems. A conserved signal transduction pathway that includes a receptor tyrosine kinase, Ras, and mitogen-activated protein (MAP) kinase regulates multiple cell fate decisions during C. elegans development. Mutations that activate similar human pathways are a frequent cause of tumors. We used a genetic screen to identify genes that are important for Ras-mediated signaling. These include core signaling proteins such as Raf, MEK and MAP kinase. We discovered new signaling proteins, such as KSR and CGR, which modulate the activity of the core signaling proteins. We identified CDF, which is involved in zinc metabolism and established an important link between zinc ions and Ras signaling. This signaling pathway regulates a transcription factor in the ETS family. We are investigating how the transcription factor is modified and regulated by sumoylation and phosphorylation. We hope to understand how extracellular signals are translated into specific cell fates during development.

The progressive, degenerative changes that occur as animals age are of fundamental importance, yet poorly understood. C. elegans is well suited for investigating aging, since it has a short life span of ~18 days. We have characterized phenotypic changes that occur as worms age, and we have identified a class of anticonvulsant drugs that delay age-related degeneration. We hope to define regulatory circuits that control aging and develop therapies that delay aging.