Molecular Engineering of Stem Cell and Gene Therapeutics

Featuring David Schaffer, Ph.D.
Professor of Chemical Engineering, Bioengineeering, and The Wills Neuroscience Institute
Associate Director, Berkeley Stem Cell Center
University of California, Berkeley

Location: 1300 Donald Bren Hall

Abstract:
New molecular therapies based on stem cells and gene delivery has significant potential for tissue engineering and repair for numerous diseases.  Before these approaches can succeed, however, a number of fundamental engineering challenges must be overcome, particularly in the nervous system, our tissue of interest.

Stem cells have significant potential for treating a wide variety of disorders, and their successful integration into such therapies will hinge upon three critical steps: their expansion without differentiation (i.e., self-renewal), their differentiation into a specific cell type or collection of cell types, and their functional integration into existing tissue.

Precisely controlling each of these steps will be essential to maximize their therapeutic efficacy, as well as minimize potential side effects that can occur when the cells numbers and types are not properly controlled.  Highly-regulated signals in the microenvironment surrounding the cells, such as soluble factor concentrations and matrix mechanical properties, have been implicated in modulating these cellular processes.  However, tight control over such proliferation and differentiation signals is rarely achieved during growth outside the body.

We combine experimental and computational approaches to understand basic mechanisms by which microenvironmental signals regulate of stem cell fate choice, including neural stem and human embryonic stem cells. Furthermore, we have applied this basic information towards the engineering of pure synthetic, bioactive hydrogel culture systems for the expansion and differentiation of stem cells, which offer significant advantages for safety and scaleability.

Furthermore, gene therapy, introduction of genetic material to the cells of a patient for therapeutic benefit, has enormous potential to synergize with stem cells to repair damaged tissue through the delivery of genes to control stem cell function.  However, the vehicles or vectors that deliver therapeutic genes still require engineering for enhanced efficiency and safety.  Our efforts are focused on modifying vehicles based on viruses at the molecular level to overcome the common dilemma faced by all: they did not evolve in nature to perform the therapeutic endeavors we ask of them.  Specifically, we are applying directed evolution approaches to overcome several challenges in vector performance, including its mass transport through tissues and cells as well as interactions with the immune system.

We hope that these capabilities can be combined to regenerate neural tissue from the effects of neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s Diseases.

About the Speaker:
David Schaffer, Ph.D., earned a B.S. in chemical engineering from Stanford University in 1993, and a Ph.D. in chemical engineering from the Massachusetts Institute of Technology in 1998. 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.