Tim Stearns, Doctoral (Program)
Current Research and Scholarly Interests
I am interested in studying centrosomes, cilia, and cell cycle regulators in differentiated cells, specifically the relationship between centrosome duplication and DNA replication.
Cyclin-dependent kinase control of motile ciliogenesis
Cycling cells maintain centriole number at precisely two per cell in part by limiting their duplication to S phase under the control of the cell cycle machinery. In contrast, postmitotic multiciliated cells (MCCs) uncouple centriole assembly from cell cycle progression and produce hundreds of centrioles in the absence of DNA replication to serve as basal bodies for motile cilia. Although some cell cycle regulators have previously been implicated in motile ciliogenesis, how the cell cycle machinery is employed to amplify centrioles is unclear. We use transgenic mice and primary airway epithelial cell culture to show that Cdk2, the kinase responsible for the G1 to S phase transition, is also required in MCCs to initiate motile ciliogenesis. While Cdk2 is coupled with cyclins E and A2 during cell division, cyclin A1 is required during ciliogenesis, contributing to an alternative regulatory landscape that facilitates centriole amplification without DNA replication.
View details for PubMedID 30152757
Mitosis sans Mitosis: The Mitotic Oscillator in Differentiation
2017; 43 (4): 385–86
Differentiation and proliferation are usually considered to be antagonistic partners in development. However, in a recent issue of Science, Al Jord et al. (2017) show that key regulators of the mitotic cycle are redeployed in differentiating multiciliated cells to promote ciliogenesis without mitotic progression.
View details for PubMedID 29161589