We are developing a research program that uses molecular and cellular engineering approaches to investigate biomedical problems. Our lab works on the molecular engineering of gene and stem cell therapies for tissue repair. In particular, we are working to improve the performance of several gene delivery vehicles and investigating the potential of an attractive gene therapy target, neural stem cells, for regenerating tissue damaged in neuro-degenerative disorders such as Alzheimer’s and Parkinson’s disease.

Gene Delivery
In the decade since the first human gene therapy clinical trial, scientists have worked to overcome a number of challenges to the success of gene therapy. These efforts have culminated in several successes in human clinical trials, including ones for hemophilia, heart disease, and cancer. Gene therapy is therefore poised to serve as a conduit to translate the knowledge gained from the human genome sequence into therapeutic benefit for society. However, significant progress must still be made before promising gene therapy strategies become therapeutic realities.

The most significant challenge in gene therapy has been the development of efficient gene delivery vehicles, or vectors. We are therefore applying principles of combinatorial chemistry and directed evolution to improve several gene delivery vectors, including adeno-associated viral (AAV), retroviral, lentiviral, and molecular conjugate vectors. We are currently attempting to engineer and evolve these vectors at the molecular level to improve their safety, delivery efficiency, and ability to target specific cell types.

Neural Stem Cells
Our second major research thrust is dedicated to understanding the biology and exploring the therapeutic potential of stem cells. We are particularly interested in neural stem cells, which have recently been shown to grow and develop into new neurons and other types of cells of the nervous system throughout our lives. These cells therefore have significant potential for repopulating tissue after the devastating effects of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease. However, we must first learn how to control these cells, that is, to understand the regulation of stem cell division and differentiation into specialized cell types such as neurons.

We are therefore interested in characterizing the genes and signaling mechanisms that regulate or communicate to a stem cell how to behave. We have identified and are characterizing a novel factor that stimulates neural stem cell proliferation using principles from chemical kinetics and process control. In parallel, we are employing a functional genomics approach to identify other signaling factors involved in controlling neural stem proliferation and differentiation. Principles learned from studying neural stem cell regulation may also apply to the other stem cell populations of therapeutic interest.

Gene and stem cell therapies represent the next generations of potentially very powerful therapeutic approaches to human disease; however, many challenges in these related fields must still be overcome. We believe that an interdisciplinary approach can continue to make progress in the improvement and optimization of these molecular and cellular therapies.

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Gene and stem cell therapies represent the next generations of potentially very powerful therapeutic approaches to human disease