How are the major transitions in the cell division cycle controlled, and how might disruptions in that control affect proliferation and genome stability? How do signaling pathways that control cell cycle progression (both intracellular and extracellular) affect DNA replication competence and regulation? Follow the link for “Research” to read more detailed background information.
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 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 they can proliferate to replace damaged or old cells. We seek to determine how cell cycle transitions are 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 (new!) 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,” inhibit enzyme activities with drugs, or overproduce proteins by transient transfection, retroviral insertion, or adenoviral infection. 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.
Follow the link for “Publications” to run an automatic search for all the lab’s papers in PubMed. (Frequent PubMed users will need to click "go" to run the search.)