 | David Schaffer Professor, Bioengineering and Chemical Engineering and Helen Wills Neuroscience Institute; Chemist Faculty, Lawrence Berkeley National Lab274 Stanley Hall, (510) 643-5963,
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http://www.cchem.berkeley.edu/schaffer/ Research Interests: Our research program employs molecular and cellular engineering approaches to investigate biomedical problems. Our laboratory is a part of the Department of Chemical Engineering, the Helen Wills Neuroscience Institute, and the Bioengineering Graduate Group at Berkeley. We are interested in the related areas stem cell bioengineering, gene delivery systems, and molecular virology, with applications in regenerative medicine and tissue engineering. We will develop a research program that employs molecular and cellular engineering approaches to attempt to investigate biomedical problems. In particular, our lab is interested in the related areas of stem cell bioengineering and gene delivery, with applications in regenerative medicine and tissue engineering. Many of our efforts are dedicated to understanding the biology and exploring the therapeutic potential of stem cells. Stem cells are immature cells that exist in various locations of our bodies. Throughout our lifetimes, these cells divide and develop into the specialized cells that perform the functions necessary for life. Therefore, if we contract a disease that kills those specialized cells, our stem cells are a potential source for replacing lost cells to counteract or even cure the disorder. There are several challenges that must be overcome in this field. In particular, efforts to engineer tissues rely upon the ability to control stem cells. That is, the signals that control stem cell function and fate must first be discovered, and then integrated into cellular microenvironments to control stem cell expansion and lineage-specific differentiation. We have efforts in novel signal discovery, computational and experimental analysis of the biological networks that cells use to interpret and implement these signals, and on the integration of these signals into synthetic, polymeric microenvironments for optimal stem cell control in collaboration with the group of Prof. Kevin Healy (Bioengineering). This blend of stem cell biology, systems biology analysis, and biomaterials engineering has led to significant advances in the application of stem cells for tissue repair. Our second major research thrust is dedicated to understanding the biology and exploring the therapeutic potential of gene delivery, which serves as an effective means to control stem cells. Gene therapy can be defined as the introduction of genetic material to the cells of an individual for therapeutic benefit. A variety of approaches are under development to use gene therapy for treating cancer, AIDS, and a number of inherited genetic disorders. For example, gene therapy could be used to replace the genes hemophilia patients are missing, to bolster the immune system to recognize and combat tumors, or to inhibit the replication of HIV virus. However, significant progress must still be made before these developing strategies become therapeutic realities. One of the most formidable obstacles to gene therapy is how to efficiently deliver genes to a sufficient number of cells to yield a therapeutic effect. A number of gene delivery vehicles, or vectors, are in development, and most exploit or emulate the abilities many viruses have evolved to deliver their genes to cells as part of their life cycles. However, while viruses have developed numerous strategies to deliver genes over millions of years of evolution, the efficiency and safety of vehicles based upon recombinant viruses must still be further improved. We have developed numerous high-throughput directed evolution approaches to engineer the properties of viral vehicles at the molecular level to enhance their abilities to deliver genes. These successful efforts are enhancing the abilities of several vectors to make them more effective at delivering gene “medicines.” In parallel, we are interested in studying some basic aspects of viral biology. Specifically, viruses have evolved gene circuits that after infecting a cell execute programs to harness cells to reproduce the virus. We apply integrated systems biology approaches, composed of computational and experimental efforts, in collaboration with the group of Prof. Adam Arkin (Bioengineering) to how the structures of these gene circuits have dynamically evolved to optimize the virus’ ability to hijack cells to maximize its ability to reproduce. This fundamental work is leading to new insights on how to combat viral infectious disease. Furthermore, we plan for these related lines of research to converge in the future. If we can effectively deliver a gene, and we can learn much more about what kinds and levels of genes are needed to control stem cell behavior, we can attempt to apply this information to longer term therapeutic goals. These aims could include using gene delivery to stimulate stem cells to divide more rapidly, to generate specific types of cells such as neurons, or to guide the successful integration of specific cell types into tissue for functional repair. It is our hope that this research will not only enhance our understanding of neuroscience, but also eventually alleviate the devastating effects of numerous diseases. |