Presenter Information

Michelle Dawson, Brown University

Location

Cherry Auditorium, Kirk Hall

Start Date

2-22-2018 12:45 PM

Description

Many of the hallmarks associated with cancer, including unlimited replicative potential, apoptotic evasion, and tissue invasion and metastasis, can be linked to abnormal cytoskeletal or matrix mechanics – important biophysical parameters. A common feature of these biophysical interactions is the transmission of force from the extracellular matrix to the internal cytoskeleton, which forms the structure of the cell. My lab recently showed that increased traction forces transmitted from the internal cytoskeleton to the external environment correlate with increased cancer cell motility, proliferation, and chemoresistance; this was demonstrated in mechanosensitive breast and ovarian cancer cells that respond to changes in matrix stiffness and in a genetic model of induced epithelial to mesenchymal transition. We also showed that paracrine factors exchanged between cancer and stromal cells dramatically alter the mechanical properties of both cell types. Mechanical forces in the primary tumor are caused by solid stress that results from the rapid proliferation of tumor cells and the recruitment of host-derived stromal cells. Matrix stiffening and high-interstitial fluid pressure further contribute to this high stress environment, which alters cells and the surrounding matrix to activate signaling pathways important in cancer. Mechanical forces are also critical in directing cancer metastasis. In fact, cancer cells undergo a cascade of biophysical changes throughout this process. Quantitative analysis of intracellular mechanics, surface traction forces, and matrix stiffness allows us to probe the biomechanical properties of the tumor with an unprecedented level of detail. These biophysical techniques can be used to systematically investigate the parameters in the tumor that control cancer cell interactions with the stroma and to identify specific conditions that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer. My presentation will focus on lessons we’ve learned through quantitative biophysical analysis of cells in the tumor microenvironment I will also discuss current research projects focused on investigating the role of stromal cell aging in cancer progression and mechanisms contributing to chemotherapy and radiation resistance.

Speaker Bio

Dr. Michelle Dawson has been an Assistant Professor of Molecular Pharmacology, Physiology, and Biotechnology at Brown University since July 1, 2016. During this time, she utilized her expertise in cell biophysics and cancer biology to establish a research lab focused on quantitative analysis of the molecular and mechanical profiles of cells in tumor and tissue microenvironments. This fundamental knowledge will guide in the development of molecular and cell-based therapeutics that can be used in regenerative medicine and cancer therapy. Her research utilizes quantitative microscopy techniques based on transport phenomena to characterize the biophysical properties of different cell types; these biophysical properties play a critical role in directing cell migration, differentiation, and development in normal tissues and tumors. This biophysical approach is combined with genomic analysis and small molecule screening to elucidate the molecular pathways important in disease. Her research at Georgia Tech laid the groundwork for her current research by developing a biophysical screening approach to profile cancer cell interactions with stromal cells, along with cell fate processes important in cancer. She previously used this approach to classify breast and ovarian cancer cells by their mechanical properties and to identify new strategies for targeting Taxol resistant cancer cells. She also showed that paracrine factors exchanged between cancer and stromal cells dramatically alter the biophysical properties of both cell types. Her research has resulted in 30+ publications, including papers in leading journals such as PNAS, Nature, Journal of Cell Science, and Scientific Reports (H-index~17).

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Feb 22nd, 12:45 PM

Tumor Microenvironment Interactions: Forcing Cancer Progression

Cherry Auditorium, Kirk Hall

Many of the hallmarks associated with cancer, including unlimited replicative potential, apoptotic evasion, and tissue invasion and metastasis, can be linked to abnormal cytoskeletal or matrix mechanics – important biophysical parameters. A common feature of these biophysical interactions is the transmission of force from the extracellular matrix to the internal cytoskeleton, which forms the structure of the cell. My lab recently showed that increased traction forces transmitted from the internal cytoskeleton to the external environment correlate with increased cancer cell motility, proliferation, and chemoresistance; this was demonstrated in mechanosensitive breast and ovarian cancer cells that respond to changes in matrix stiffness and in a genetic model of induced epithelial to mesenchymal transition. We also showed that paracrine factors exchanged between cancer and stromal cells dramatically alter the mechanical properties of both cell types. Mechanical forces in the primary tumor are caused by solid stress that results from the rapid proliferation of tumor cells and the recruitment of host-derived stromal cells. Matrix stiffening and high-interstitial fluid pressure further contribute to this high stress environment, which alters cells and the surrounding matrix to activate signaling pathways important in cancer. Mechanical forces are also critical in directing cancer metastasis. In fact, cancer cells undergo a cascade of biophysical changes throughout this process. Quantitative analysis of intracellular mechanics, surface traction forces, and matrix stiffness allows us to probe the biomechanical properties of the tumor with an unprecedented level of detail. These biophysical techniques can be used to systematically investigate the parameters in the tumor that control cancer cell interactions with the stroma and to identify specific conditions that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer. My presentation will focus on lessons we’ve learned through quantitative biophysical analysis of cells in the tumor microenvironment I will also discuss current research projects focused on investigating the role of stromal cell aging in cancer progression and mechanisms contributing to chemotherapy and radiation resistance.