Engineering Cancer Cell Migration.
TITLE:
Engineering Cancer Cell Migration.
DATE:
Friday, October 11, 2019
TIME:
3:30 PM
LOCATION:
GMCS-314
SPEAKER:
Dr. Stephanie Fraley, Assistant Professor, Bioengineering Department, University of California-San Diego
ABSTRACT:
Metastasis is the primary cause of cancer related deaths. The migration of cancer
cells from their tissue of origin to other tissues in the body is central to the
metastatic process. Efforts to control the spread of cancer will require a predictive
understanding of how metastatic migration is extrinsically and intrinsically regulated.
My lab is working to reach this level of cell migration engineering by addressing three
core knowledge gaps: (1) how is migration differentially regulated by microenvironmental
context, (2) what is the source of migration heterogeneity among cells of the same type
in the same context, and (3) how can we link migration phenotype to genotype to identify
key molecular regulators despite extensive heterogeneity. We have developed three new
approaches to address these questions. First, to deepen our understanding of migration
regulation by the collagen-rich tumor microenvironment, we have developed a technique to
tune collagen architecture independently of density and stiffness. We find that collagen
architecture regulates oxidative and metabolic stress by tuning adhesion strength, and
that adhesion strength is directly related to matrix degradation. Next, we integrate four
quantitative microscopy techniques to measure the core processes driving migration
simultaneously in single cells. This is unveiling the way in which subcellular processes
integrate to produce whole cell migration behaviors and is being used to model and predict
migration heterogeneity. Finally, we employ a photoconversion scheme to enable ”laser
tagging” of cells based on migration phenotype for subsequent cell sorting and molecular
analysis. Through this approach, we show that migration-phenotype-based clustering of
single-cell RNA sequencing data reveals unique insight into molecular regulators of migration
as well as the different metabolic and immune regulatory states of cancer cell subpopulations.
Biography: Dr. Stephanie Fraley joined UC San Diego in July 2014 as an assistant professor of
Bioengineering. Her research takes a multidisciplinary and multi-scale approach to (1) understand
mechanisms of cell migration underlying human disease, in particular cancer, and (2) develop clinical
profiling technologies for improved understanding and treatment of human diseases. She earned her B.S.
in Chemical Engineering in 2006 from The University of Tennessee Chattanooga and her Ph.D. in Chemical
and Biomolecular Engineering in 2011 from The Johns Hopkins University. For her graduate work, she was
awarded an NSF Graduate Research Fellowship, National Tau Beta Pi Fellowship, and was an Achievement
Rewards for College Scientists Scholar, Johns Hopkins Heath Fellowship, National Siebel Scholarship,
and ASEE/NSF Engineering Innovations Fellowship. Dr. Fraley then joined the Emergency Medicine department
at The Johns Hopkins University as a postdoctoral fellow where she developed novel technological approaches
to sensitively detect and quantitatively identify genetic material circulating in the bloodstream. Recently,
she received a National Burroughs Wellcome Fund Career Award at the Scientific Interface for her research
merging clinical diagnostic and basic research approaches. She is also a SAGE Bionetworks Scholar, Kavli
Frontiers of Science Fellow, BMES CMB Rising Star awardee, and recipient of an NSF CAREER award.
HOST:
Parag Katira, Department of Mechanical Engineering
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