Solid tumors transition to invasion and therapy resistance through the cooperation and competition of heterogeneous single cell phenotypes. However, the emergence of robust collective behaviors from complex interactions within the dynamic tumor ecosystem remain poorly understood. My research investigates coordinated cell migration in space and time using live cell imaging, 3D biomaterials, and microfluidic devices. First, I investigate how mammary epithelial cells transition from a fluid-like “unjammed” phase to a solid-like “jammed” phase. I show that these collective behaviors exhibit striking analogies with a gelation-like mechanism during the diffusion limited aggregation of non-living colloidal particles. Second, I analyze the disorganization and dissemination of multicellular clusters cultured in 3D matrix, which exhibit both collective and individual invasion phenotypes with distinct traction signatures. Finally, I investigate how mixed subpopulations with distinct migration phenotypes invade microfluidic 3D biomaterials. Strikingly, I find that a small subset of highly invasive “leader cells” can dominate the overall invasion kinetics and the escape to nearby vessels. Altogether, my development of next-generation bioengineering technologies for cancer biology enable new insights into the mechanobiology of tumor invasion and potential therapeutic targets. My future work will apply these tools to characterize patient-derived tumor tissue and generate a personalized atlas of cancer progression for individual patients, which could complement existing clinical measures to aid in the development of precision medicine approaches.
Dr. Susan E. Leggett is an NCATS TL1 Postdoctoral Fellow in Chemical and Biological Engineering at Princeton University, and her research interests lie at the interface of bioengineering and cancer biology. She has pioneered innovative technologies for precision measurement of single cell morphology, collective migration, as well as traction force microscopy in 3D matrix. Dr. Leggett received her B.S. in Biochemistry with a minor in Mathematics from the University of Vermont in 2013. She earned her Ph.D. in Pathobiology at Brown University in 2018, advised by Prof. Ian Wong in the School of Engineering. Dr. Leggett then moved to her current postdoctoral position at Princeton with Prof. Celeste Nelson. Dr. Leggett has been nationally recognized as a 2021 BME Rising Star in Engineering in Health by Columbia and Johns Hopkins, as well as the 2021 Chemical Engineering Future Faculty Series of Northeastern and Princeton.
