Molecular Elucidation and Engineering of Stem Cell Microenvironments
Dr. David Schaffer, Professor of Chemical Engineering, Department of Bioengineering, and the Helen Wills Neuroscience Institute, Co-Director, Berkeley Stem Cell Center, University of California, Berkeley
Thursday, January 21 at 2010, 2-3 PM EST
Download the slides and Q&A here.
The archived webinar here.
About this Webinar
Stem cells are defined by their capacities for self-renewal and differentiation into one or more cell lineages, and these processes are regulated by signals from the stem cell microenvironment, or niche, in various tissues throughout organismal development and adulthood. These niches control cell function by presenting complex, regulatory signals including soluble small molecules and proteins, extracellular matrix (ECM) signals, and mechanical cues. There has been considerable progress in studying soluble signal regulation of stem cell function, but comparatively less work has been focused on investigating the “solid phase” of the microenvironment, in large part due to experimental complexities in studying large matrix and other proteins. Recent work demonstrates that bioactive, synthetic materials (i.e., matrices, scaffolds, or culture substrates) can be harnessed to emulate and thereby study the effects of solid phase, or biophysical, signals on stem cell function. We have harnessed biomaterials to investigate a number of aspects of the stem cell microenvironment and have found that extracellular mechanical properties, or stiffness, can profoundly impact neural stem cell self-renewal and differentiation into neurons vs. glia, and mechanistic analysis implicates Rho GTPases as key “mechanotransducers” in this process. Furthermore, immobilization of biochemical signals in the solid phase of a natural niche, including extracellular matrix motifs as well as matrix-binding growth factors, can lead to nanoscale organization of these signals that can modulate signal transduction by controlling cellular receptor clustering. We have developed a hybrid system composed of growth factors oligomerized with a synthetic material and find that nanoscale organization of signaling molecules can profoundly modulate their bioactivity and potency, for example in regulating the proliferation of neural stem cells and the neuronal differentiation of human embryonic stem cells. Finally, we have found that the combinatorial presentation of different motifs from individual extracellular matrix proteins from a material can generate synthetic systems capable of supporting the self-renewal and differentiation of both neural stem cells and human embryonic stem cells, thereby enabling the dissection of the ECM into key individual signals necessary to support stem cell function. Biomimetic materials therefore represent systems that can be used to study principles by which the solid phase of a stem cell microenvironment regulates cell function, as well as offer safe and scaleable systems to precisely control stem cell function for biotechnological and biomedical application.
David Schaffer Biosketch
David Schaffer is a Professor of Chemical Engineering, Bioengineering, and Neuroscience at University of California, Berkeley, where he also serves as the Co-Director of the Berkeley Stem Cell Center. He graduated from Stanford University with a B.S. degree in Chemical Engineering in 1993. Afterward, he attended Massachusetts Institute of Technology and earned his Ph.D. also in Chemical Engineering in 1998 with Professor Doug Lauffenburger. Finally, he did a postdoctoral fellowship in the laboratory of Fred Gage at the Salk Institute for Biological Studies in La Jolla, CA before moving to UC Berkeley in 1999. At Berkeley, Dr. Schaffer applies engineering principles to enhance stem cell and gene therapy approaches for neuroregeneration. This work includes mechanistic investigation of stem cell control, as well as molecular evolution and engineering of viral gene delivery vehicles. David Schaffer has received an NSF CAREER Award, Office of Naval Research Young Investigator Award, Whitaker Foundation Young Investigator Award, and was named a Technology Review Top 100 Innovator. He was also awarded the American Chemical Society BIOT Division Young Investigator Award in 2006, the Biomedical Engineering Society Rita Shaffer Young Investigator Award in 2000, and was elected to the College of Fellows of the American Institute of Medical and Biological Engineering in 2008.