Associate Professor, Biology
Cancer Cell Biology
Area of Interest
Cancer often manifests as a disease of mis-regulated cell division. Our contributions to the field of cancer cell biology are primarily in defining molecular and physical mechanisms of the final step of cell division: cytokinesis. Proper execution of cytokinesis, the physical division of one cell into two, is critical for maintaining ploidy and genome stability. Failure of cytokinesis can cause tetraploidy, which is an intermediate in, and therefore risk for, cancerous transformation. On the other hand, repeated cytokinesis failure erodes cell viability; compounds targeting cytokinesis could serve as anti-mitotic cytotoxic chemotherapeutics. Our advances in the fundamental bases of cell division will thus enhance understanding of both cancer initiation and the potential for novel drugs.
We study cytokinesis by applying a combination of cell and developmental biology, mathematical modeling, advanced statistics, genetics, and biochemistry. Our recently-published and ongoing work uncovered mechanisms of cytoskeletal regulation and organization. We discovered novel cytokinetic ring proteins and defined their roles in negative feedback on the master regulator RhoA. We also showed that molecular motor ensembles, as well as non-motor crosslinkers both drive and brake cytoskeletal remodeling in non-muscle contractility. Our most exciting ongoing work reveals that pulsed RhoA activity causes the cytoskeleton to undergo vibrations in a subharmonic series.
The above-mentioned cytokinesis work is largely done using the C. elegans zygote as a powerful model cell type for cell-autonomous, in vivo biology. Genome editing, graded protein depletions, and quantitative imaging are all exceptionally accessible in C. elegans, and homologues to human regulatory and structural proteins are expressed and required. We also study variations on the theme of cell division in C. elegans using a simple (one dimensional!) epithelium (the vulval precursor cells), and the syncytial germline. The latter is a fascinating cancer model, as dysregulation of its intrinsic mitosis-to-meiosis differentiation leads to tumors. Importantly, agent- or particle-based modeling is another powerful experimental system we employ. We use and also help develop the Cytosim modeling platform for explicit depiction and tracking of the physically realistic stochastic behaviors of cytoskeletal components and cellular surfaces. Our application of both C. elegans as a model for cell and developmental biology, and of agent-based modeling make us versatile, nimble and willing collaborators and colleagues.
Awards and Honors
- Marine Biological Labs Whitman Fellow, summer 2020 (deferred)
- Elected to Marine Biological Labs Science Council
- Appointment as standing member of NIH NIGMS study section, Nuclear and Cytoplasmic Structure and Dynamics
- William C. Friday Award for Excellence in Undergraduate Teaching, UNC-Chapel Hill, 2018