The leading edge of the non-tumorigenic MCF10A progresses smoothly forward over time (left), while the metastatic MDA-MB-231 cells (right) have a disordred progression over time. Scale bar indicates 100 micrometers. During metastasis, cancer spreads to secondary locations in the body, forming new tumors that are difficult to treat. The dynamics of cells during this process provides a fascinating physical system with immediate relevance. Currently, I am focused on the dynamics of cell migration during breast cancer metastasis. In ongoing research, we are studying how collective interactions between cells change in response to oncogenic mutations.
As a Postdoctoral Fellow in the lab of Stuart Martin in the Marlene and Stewart Greenebaum Comprehensive Cancer Center at the University of Maryland School of Medicine, I have also had the opportunity to collaborate with several researchers on other aspects of breast cancer metastasis. In collaboration with Stephan Pratt of the Martin lab, I've developed analysis tools to measure calcium signaling in response to mechanical stimuli. With Patrick Bailey, I helped develop statistical analysis tools to understand the growth of clonal mammospheres.
- R. M. Lee, M. I. Vitolo, W. Losert, and S. S. Martin. Distinct Roles of Tumor Associated Mutations in Collective Cell Migration. Scientific Reports 11(1):10291, 2021. 10.1038/s41598-021-89130-6.
- S. J. P. Pratt, R. M. Lee, K. T. Chang, E. O. Hernández-Ochoa, D. A. Annis, E. C. Ory, K. N. Thompson, et al. Mechanoactivation of NOX2-Generated ROS Elicits Persistent TRPM8 Ca2+ Signals That Are Inhibited by Oncogenic KRas. Proceedings of the National Academy of Sciences 117(42):26008–19, 2020. 10.1073/pnas.2009495117.
- S. J. P. Pratt, E. O. Hernández-Ochoa, R. M. Lee, E. C. Ory, J. S. Lyons, H. C. Joca, A. Johnson, et al. Real-Time Scratch Assay Reveals Mechanisms of Early Calcium Signaling in Breast Cancer Cells in Response to Wounding. Oncotarget 9(38):25008–24, 2018. doi:10.18632/oncotarget.25186
- P. C. Bailey, R. M. Lee, M. I. Vitolo, S. J. P. Pratt, E. Ory, K. Chakrabarti, C. J. Lee, K. N. Thompson, and S. S. Martin. Single-Cell Tracking of Breast Cancer Cells Enables Prediction of Sphere Formation from Early Cell Divisions. iScience 2018. doi:10.1016/j.isci.2018.08.015
Phase contrast image of migrating MCF10A cells (human epithelial cells) overlaid with a particle image velocimetry (PIV) flow field. Scale bar indicates 100 micrometers. In my PhD thesis work, I studied changes in cell migration behavior during cancer progression, and in particular, how this migration changes in large collective groups. We developed quantitative image analysis techniques that allowed us to study cell migration using nonlinear dynamics tools that were developed to study physical systems such as fluid flows or sheared grains. These methods are discussed in our publication in the New Journal of Physics focus issue on the Physics of Cancer.
We used image processing and analysis tools we developed to study cells of varying malignancy. Studying varying cell lines will allow us to understand how physical forces in the cells' environment (such as cell-cell adhesion) change collective migration behavior. Our work on the role of E-cadherin (a cell-cell adhesion molecule) was published in Convergent Science Physical Oncology. We further used our tools to study how migration behavior changes over long distances. Our modeling work, published in the Journal of the Royal Society, Interface, suggests that persistence of cell polarity may play an important role in collective cell migration.
- R. M. Lee, D. H. Kelley, K. N. Nordstrom, N. T. Ouellette, and W. Losert. Quantifying stretching and rearrangement in epithelial sheet migration. New Journal of Physics, 15(2):025036, 2013. doi:10.1088/1367-2630/15/2/025036
- R. M. Lee, C. H. Stuelten, C. A. Parent, and W. Losert. Collective cell migration over long time scales reveals distinct phenotypes. Convergent Science Physical Oncology, 2:025001, 2016. doi:10.1088/2057-1739/2/2/025001
- R. M. Lee, Guided Migration and Collective Behavior: Cell Dynamics during Cancer Progression. Digital Repository at the University of Maryland (Thesis), 2016. doi:10.13016/M2D81H
- R. M. Lee, H. Yue, W. Rappel, and W. Losert. Inferring Single-Cell Behaviour from Large-Scale Epithelial Sheet Migration Patterns. Journal of The Royal Society Interface 14(130):20170147, 2017. doi:10.1098/rsif.2017.0147
- R. M. Lee and W. Losert. Dynamics Phenotyping across Length and Time Scales in Collective Cell Migration. Seminars in Cell & Developmental Biology, SI: Viscoelasticity, 93:69-76, 2019. doi:10.1016/j.semcdb.2018.10.010