My research interests involve the biochemical and genetic
study of conserved signaling pathways involved in critical cell fate decisions
and cancer development using the nematode
Caenorhabditis elegans
as a model system. Signal transduction pathways that include a receptor
tyrosine kinase (RTK), Ras, and MAP kinase have been highly conserved during
metazoan evolution and regulate many different cell fate choices during
the development of vertebrates, C. elegans, and Drosophila melanogaster.
Mutations that affect genes in this signaling pathway are a common cause
of human tumors. Furthermore, 10-15% of the most common human tumors contain
activating mutations of the Ras gene. An important unanswered question
is how these pathways trigger specific cell fates in particular developmental
contexts.
The Ras signaling pathway functions at multiple
times during C. elegans development. It has been characterized most
extensively during the formation of the hermaphrodite vulva, a specialized
epidermal structure used for egg-laying. While the core components of the
Ras signaling pathway have been identified through genetic analyses in
C.
elegans and other model organisms, there is little known regarding
how downstream molecules in this pathway effect a particular cell fate.
I have chosen to investigate this aspect of developmental specification
via signal transduction pathways by identifying mutations in genes involved
in vulval development downstream of known core components (at the transcription
factor level). These studies have identified a molecule with oncogenic
properties involved in vesicle secretion that has not previously been implicated
in Ras-signaling. In addition, using the C. elegans genome
sequence, we can predict novel MAP kinase substrates and characterize them
biochemically. |
