Research Topics
Department of Chemical and Biomolecular Engineering
Ph.D. California Institute of Technology
Research Topics
Research Interests
Molecular bioengineering of advanced drug delivery systems. The overall goals of our research program are to use engineering principles to understand the obstacles to safe, efficient and effective drug delivery and to use an engineering approach to design advanced drug delivery systems. For example, as medications have advanced from traditional small-molecule drugs to protein therapeutics and most recently to genetic materials, more sophisticated methodologies are required to ensure delivery of the therapeutic agent to the proper site within the body, at appropriate concentrations, with the required regulation, and without damage to the drug.
Protein and peptide therapeutics are often encapsulated in biodegradable polymer devices, such as microspheres, from which the drug is released over time as the microspheres erode in the body. These "controlled-released" strategies have been investigated for several decades, and commercialized products are now on the market. In one project, we are expanding the potential of controlled-released drug delivery using a unique technology for fabrication of micro- and nano-particles with precisely controlled sizes, size distributions and 3D architectures (developed by Prof. Kevin Kim, Department of Electrical and Computer Engineering). Our goal is to utilize the unprecedented control of particle size and morphology afforded by Kim’s technology to produce devices tailor-made for advanced drug delivery applications such as passive targeting based on particle size and generation of complex release-rate profiles. Other projects include development of surface-labeled nanoparticles for drug delivery to the brain and magnetic nanoparticles for bioimaging.
A second major focus of our group is the design and synthesis of improved materials for human gene therapy - the use of genetic material for treatment of human diseases from cystic fibrosis to cardiovascular disease to cancer. While the field is advancing rapidly, a primary hurdle to development of human gene therapy is a lack of safe and efficient methods for delivery of genetic material. Our approach to creating novel gene delivery materials is two-fold. First, we are using directed molecular evolution to re-engineer viruses, nature's gene delivery vehicles, to make them more suitable as human therapeutics. This approach comprises randomly mutating the viruses and selecting for those with improved properties under a desired set of conditions. A major advantage of directed evolution is that it allows us to enhance properties needed for therapeutic applications (e.g., cell-specific targeting, stability during purification and storage, etc.) while maintaining the virus' capacity for highly efficient gene delivery. Secondly, we are creating new vectors based on synthetic materials. In comparison with viruses, synthetic vectors have several advantages that will make them the gene delivery method of choice in the long run. For example, polymer-based vectors are potentially non-toxic and non-immunogenic, are more stable and simpler to produce and purify in large quantities, and through careful design can be made to exhibit a very wide range of desirable properties. To generate such polymers, our approach is to first develop quantitative understanding of the structure-function relationships of currently available vectors. We then use the resulting database of information to design new chemistries and to construct novel architectures for generation of safe and highly efficient "artificial viruses."
Key Words Gene
Therapy, Directed Molecular Evolution, Retrovirus, Polycations, Drug Delivery,Biopolymers, Microspheres, Microcapsules, Nanoparticles
Current Research Funding
American Cancer Society, American Heart Association, National Institutes of Health, National Science Foundation