Cram Lab

Research Description

Interactions between cells and their extracellular environment play an essential role in controlling tissue architecture, cell survival, and cell migration. These processes are important for normal animal development and are disrupted during cancer progression.

Integrins are cell surface proteins that sense the extra cellular protein (matrix) environment and signal to the cell to control differentiation, survival and migration of cells. In animals there are multiple integrins with specialized and overlapping roles in various cell types.

The nematode, C. elegans, has only two integrins, and is an excellent system for genetic and molecular analysis of integrin signaling in vivo. In C. elegans, integrins are essential for embryonic development, muscle cell adhesion and contraction, axon outgrowth, and migration of the distal tip cells (DTC).

I have recently found more than 100 C. elegans genes that regulate DTC migration many of which function in integrin signaling. Our goal is to understand how genes cooperate to control cell migration in vivo. We are using data mining to find interacting networks of genes, analysis of expression patterns, and cell-specific RNAi to disrupt genes in the DTC, in other migratory cells, and in surrounding tissues. In addition, using various nematode strains with disrupted integrin function, we hope to identify new genes that genetically interact with integrins in migratory cells.

One of the most exciting outcomes of my DTC migration screen was the isolation of new regulators of cell migration. We are studying the genetic and biochemical interactions of several of these genes using C. elegans and mammalian cell culture. Our long-term research objectives involve characterization of the evolutionarily conserved mechanisms underlying cell migration, and the implications of these processes in cancer and metastasis.