For the last 7 years, our laboratory has been evaluating ionizing radiation and sphingolipid signaling in the nematode C. elegans. In many instances where mammalian systems are too complicated to obtain clear information concerning signaling pathways, C. elegans has been instructive. Mammalian systems often have multiple isoforms of an enzyme; whereas C. elegans may possess a single form. Further, mammalian tissue diversity has many times resulted in the utilization of signaling proteins in a combinatorial manner. The simplicity of the C. elegans system coupled with the capacity to readily incorporate more than 1 mutated allele in a single animal make this model ideal for asking questions regarding the molecular ordering of signaling cascades.
Our laboratory has focused on conserved genes involved in the sensing of radiation damage and the signaling of apoptotic and post-mitotic (reproductive) death. In particular, we study C. elegans, p53, abl, mitogen-activated protein kinases, sphingomyelinases, and checkpoint genes as they relate to death induction in response to ionizing radiation. We are beginning to define specific genes that distinguish post-mitotic death from apoptotic death cascades at the tissue level in C. elegans. Emphasis is on translating genetic results into animal and human models of cancer therapy.
