DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

The mechanism of cytokinesis, the final step in cell division, remains a major unsolved question in biology. We aim to understand how cells regulate and perform cytokinesis because it will give us insights into what goes wrong when cytokinesis fails and how failure and subsequent aneuploidy might be a cause or consequence of cancer. Our long-term goal is the systematic dissection of temporal and spatial control during cytokinesis. It has traditionally been challenging to study cytokinesis because it is a rapid process and many proteins also perform important functions earlier in the cell cycle. This is why small molecules, which act rapidly and with high temporal control, are ideal tools to study cytokinesis, but few active small molecules exist. We performed a screen to identify small molecule inhibitors of cytokinesis and are investigating several molecules with different and novel mechanisms of action. A major technological interest in the lab is the combination of RNAi and small molecule approaches. We are applying this strategy to discover small molecules that affect the Rho pathway, a key regulator of cytokinesis and other cellular processes. In addition to being useful tool compounds, our compounds may catalyze the development of cancer drugs.

Publications

• Eggert US, Field CM, Mitchison TJ.Small molecules in an RNAi world.Mol Biosyst 2006 Feb;2(2):93-6.
  16880926
• Eggert US, Mitchison TJ, Field CM.Animal cytokinesis: from parts list to mechanisms.Annu Rev Biochem 2006;75:543-66.
  16756502
• Eggert US, Kiger AA, Richter C, Perlman ZE, Perrimon N, Mitchison TJ, Field CM.Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets.PLoS Biol 2004 Dec;2(12):e379.
  15547975