- Cancer Cell Biology
- Associate Professor
- UNC-Chapel Hill
- 3062 Genetic Medicine Chapel Hill, NC 27599
Area of Interest
Integrating DNA replication control with checkpoint signaling.
Our lab studies the regulation of DNA replication licensing, which is the process that renders individual chromosomal segments competent to be duplicated. Licensing involves the loading of a poised but inactive DNA helicase complex at replication origins during G1. The helicase is then activated during S phase, but new loading is blocked for the remainder of the cell cycle or under conditions of acute cellular stress. For example, if the DNA is damaged, specific loading proteins are inhibited or degraded. Cells employ many "checkpoint" signaling pathways to coordinate replication licensing with progression through the cell division cycle and with a wide variety of extracellular and intracellular signaling pathways. We seek to understand how origin licensing control is linked to these signaling pathways. It's clear that cancer cells have mutations that disrupt cell cycle checkpoints, but we still don't fully understand how those checkpoints are supposed to operate in normal cells.
We manipulate various replication and checkpoint proteins in human cell lines using a variety of molecular genetic tools. We deplete proteins from cells using siRNA techniques, overproduce proteins using recombinant plasmid or viral vectors, and inhibit activities with pharmacological reagents. Ultimately we hope to achieve a greater understanding of normal cell cycle control, so that future tools for cancer diagnosis and therapy can be developed.
Awards and Honors
Recipient of the Jefferson-Pilot Fellowship in Academic Medicine