Our research group employs molecular and cellular engineering approaches to investigate biomedical problems. We are interested in the related areas of stem cell bioengineering, gene delivery systems, and molecular virology, 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 organismal development and adult tissue function. Furthermore, 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. However, 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 biomaterial microenvironments for optimal stem cell control.
Scalable expansion and differentiation of pluripotent stem cells can greatly benefit many biological applications, including cell replacement therapy, disease modeling, in vitro organogenesis and drug screening, which typically require a large numbers of readily available cells. To this end, we are interested in engineering novel three-dimensional biomaterial platforms to facilitate large-scale compatible expansion and central nervous system (CNS) directed differentiation of pluripotent stem cells. Concurrently, our efforts shed new light on potential mechanistic effects of biomaterial properties on stem cell fate.
This blend of stem cell biology, systems biology analysis, and biomaterials engineering has led to significant advances in the application of stem cells for a variety of applications including 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.”