Friday, October 11, 2013 - 2:00pm
Fung Auditorium | Powell-Focht Bioengineering Hall
Michelle R. Dawson
Assistant Professor of Chemical and Biomolecular Engineering
Georgia Institute of Technology
Biomechanical Interactions of Stem Cells and Cancer Cells in the Tumor Microenvironment
My research combines molecular and gene expression analysis with quantitative biophysical analysis using sensitive mechanical tools (such as time-lapsed cell tracking, traction force microscopy, and particle tracking microrheology) to provide genetic and mechanical profiles of tumor and stromal cells in conditions that more closely mimic the tumor microenvironment. This approach has recently been used to demonstrate that ovarian cancer cells, which metastasize to the soft omentum fat pad, preferentially engraft on adipose-mimetic substrates or MSCs differentiated into soft adipocytes. Moreover, after engrafting they display a gene expression signature characteristic of epithelial-mesenchymal transition with corresponding increases in motility, proliferation, and chemoresistance. Though this preference for soft matrices is in contrast to what has been documented in breast and other cancers, our studies have confirmed that an increased malignant phenotype is still associated with higher traction forces. Work from my lab has also shown that both murine and human MSCs undergo dramatic cytoskeletal stiffening in response to pro-migratory molecules in the tumor microenvironment, including a cocktail of molecules released by tumor cells in culture and individual molecules like TGF-1 and PDGF. The degree of stiffening is a key differentiating factor between MSCs and their less migratory fibroblast counterparts and even predictive of decreased MSC function with extended culture.
Mechanical properties of cells in the tumor microenvironment are dramatically altered by physical or chemical cues. These mechanical changes lead to differences in gene or protein expression and even cell function. Biophysical tools can be used to improve our understanding of how these factors contribute individually or collectively to the development of a malignant tumor microenvironment.
Dr. Michelle Dawson has been an Assistant Professor in the School of Chemical & Biomolecular Engineering since November 1, 2008. She holds appointments in the Bioengineering Graduate Program, the Institute for Bioengineering and Bioscience, the School of Biology, and the Wallace H. Coulter Department of Biomedical Engineering. Dr. Dawson’s research focuses on engineering stem cell-based therapeutics for use in gene therapy, tissue engineering and regenerative medicine. Molecular and genetic techniques are used in her research for the development of genetically engineered stem cells that express high levels of therapeutic proteins. The transport of stem cell-based therapeutics to diseased tissues is limited by cell migration through biological tissue barriers. Biophysical techniques, including traction force microscopy, multiple particle tracking microrheology, and intravital microscopy, are used to characterize normal and pathological cell and matrix mechanical properties. The mechanical properties of cells and their extracellular matrices are important in many cellular processes, including cell migration, differentiation, and division. This information will be used to guide the rationale development of stem cell-based therapeutics that can overcome biological transport barriers.