Why do we care?
We are intensely curious about the eukaryotic cell cycle and how it is coordinated such that the chromosomes are fully duplicated only at the appropriate time and then segregated to the two daughter cells. We wonder how cells manage to ensure that replication doesn’t occur under inappropriate circumstances, and how cell proliferation is controlled during development and maintenance of an adult organism. It's becoming increasingly clear that cancer cells initiate DNA replication inappropriately and furthermore, that they do a "sloppy" job of precisely duplicating and segregating their genomes. On the flipside, we want to know how cells ensure that cell cycle transitions are efficient so that proliferation replaces damaged or old cells. We seek to determine how the cell cycle is normally controlled and how that control is disrupted in disease.
How do we figure it out?
We use a combination of biochemistry, cell biology, molecular biology, pharmacology, quantitative live and fixed cell microscopy, and genetics. We use cultured mammalian cells (both cancer cell lines and normal cells) and manipulate the proteins and signaling activities in those cells. We suppress expression of replication and signaling proteins by RNAi “knockdown,” perturb enzyme activities with chemical inhibitors, or overproduce proteins to test their effects on cell cycle parameters. We measure protein abundance, chromatin localization, cell cycle progression, replication activity, protein-protein interactions, etc… We have active collaborations with many other cell cycle and DNA metabolism labs both at UNC and at other institutions.
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