Seminar: Deconvolving tumor dynamics

Dr. Lance Munn, Harvard University

All dates for this event occur in the past.

E001 Scott Lab
E001 Scott Lab
201 W. 19th Ave.
Columbus, OH 43210
United States

Abstract:

During tissue development, the collective organization single cells results in well-defined compartments that are separated by physical and biochemical barriers. This organization establishes the correct microanatomy (the spatial relationships between cells and with matrix components) that is maintained in the adult tissue, but often disrupted in diseases such as cancer. The self-assembly and homeostasis of the tissue structures are not only guided by biochemical pathways, but also by mechanical signals transmitted through structural components and fluids. Unfortunately, little is known about the mechanisms used by cells to participate in coordinated, collective behavior, or how these mechanisms fail in pathologies. Using microfluidic devices, mathematical models and intravital microscopy, we investigate how cells in various mechanical and chemical environments interact and cooperate to accomplish such varied goals as cancer invasion, morphogenesis and regulation of vascular function.

For example, forces exerted by flowing fluids provide important signals for the vascular endothelium. Blood flow exerts shear stresses on vessel wall cells that drive blood vessel contraction or dilation to optimize flow through a network, and plasma exchanged between vessels can coordinate sprouting angiogenesis.  Similarly, lymphatic pumping – a process central to immune function and fluid homeostasis – is sustained by cycles of fluid flow and shear stress-activated nitric oxide production. Mechanical signals can also affect tissue microanatomy: compressive forces that form as a tumor grows in a confined space can induce polarization and collective migration of the cancer cells. All of these processes involve the integration of mechanical signals by cells to direct biological processes. This interface between the collective behavior of cells and mechanobiology is relatively unexplored, but contains many potential new targets for controlling tumor progression and vascular function.

About the Speaker:

Originally trained as a chemical engineer, Dr. Munn received his PhD in Bioengineering from Rice University in 1993. He is currently Associate Professor, Director of the Bioengineering, Microscopy and Computing Core, and Deputy Director of the Steele Lab for Tumor Biology at MGH. Dr. Munn has been studying vascular biology in the context of tumor physiology for the past 20 years, with a focus on vessel microanatomy and biomechanics.  His group uses a combination of in vivo techniques, mathematical modeling and microfabrication to determine how cells cooperate to form and maintain tissues. Using these approaches Dr. Munn’s group has identified and characterized the role of mechanobiology in tumor invasion, lymphatic drainage and neovascularization.

https://steelelab.mgh.harvard.edu/lance_munn/pi_bio

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