Chemical approaches to cell division
The overall goal of our lab is to use chemical biology approaches to study cytokinesis, the final step in cell division. We are interested both in the role of naturally occurring small molecule metabolites such as lipids, and in developing and using new small molecule probes. In addition to being useful tool compounds, our compounds may catalyze the development of cancer drugs.
We discovered promising small molecule inhibitors of cytokinesis by high-throughput screening are investigating several molecules with different and novel mechanisms of action. We use a variety of approaches, including live and fixed imaging, biochemistry and organic chemistry in these studies.
We are excited about developing chemical tools to study biological pathways in addition to small molecules that affect entire processes (such as cytokinesis). The Rho pathway is responsible for regulating many important cellular events, including cytokinesis. We have combined chemical screening with RNAi to develop small molecules affect the Rho pathway and have identified several exciting candidate molecules. In addition to using these compounds to probe cytokinesis, we are planning to study their effect on other processes regulated by the Rho pathway, such as determination of cell shape or size and cell movement.
It is known that some lipids localize to the cleavage site and that membrane transport is required to relieve cortical tension during cytokinesis. However, the precise role and mechanism of this essential membrane retrieval are unknown, as is the nature of the lipids and proteins involved. We are using mass spectrometry to investigate which lipids are involved in cytokinesis. In parallel, we are using chemical and RNAi perturbations to understand the how specific lipids or lipid families participate in cytokinesis.
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