Stem cells are attractive cell sources for regenerative medicine due to their unique capacity of self-renewal and differentiation into multiple lineages. To fully realize the therapeutic potential of stem cells, it is critical to understand the mechanisms by which they receive information from the microenvironment and how such interactions alter the stem cell functions. The results of such studies can then aid in the synthesis of culture microenvironments that emulate stem cell niche in vivo, and would have broad applications in areas such as tissue regeneration and drug/gene delivery. In addition to their potential as cell sources for tissue regeneration, stem cells also hold great promise for targeting and delivering therapeutic molecules to treat both inherited and acquired diseases.

Fundamental: Understand how microenvironmental cues regulate stem cell fate

Stem cell functions are regulated by local cues present in their microenvironment including soluble growth factors, extracellular matrix (ECM), cell-cell interactions, as well as mechanical signals such as the matrix rigidity. While the effect of individual type of microenvironmental cues on stem cell behavior has been studied in great depth, little is known about how the complex interplay of multiple types of signals would influence stem cell behavior. We are interested in understanding the effects of interactive signaling on stem cell in 3D and results from such studies would help predict stem cell phenotype in vivo and direct rational design of stem cell niche for tissue engineering applications.

Technological: Develop controlled delivery system to direct stem cell differentiation in situ

Advances in gene therapy provide a powerful tool to promote lineage-specific differentiation via directly regulating the intrinsic signals of stem cells. Today, technology is being developed with the potential to either "turn on" a target gene, through DNA delivery, or "turn off" a gene by siRNA delivery. However, such therapy has rarely found its way into the clinic due to the lack of safe and efficient delivery systems that can stably regulate stem cells in vivo. Our goal is to develop a controlled release system for sustained delivery of synergistic genetic signals to direct stem cells differentiation in situ.

Translational: Stem cells for targeting and delivery of therapeutic factors

Many disease processes are associated with abnormal blood supply, cell death and eventual loss of tissue structure and function. Delivery of therapeutic factors directly to the affected tissues may intervene with the disease progression and start the tissue repair. However, effective targeting and delivery to the disease site remains a great challenge. We are interested in engineering stem cells for targeting and delivery of therapeutic factors to restore normal vascularization and promote tissue regeneration. Findings from such study would have great translational potential that may benefit patients in the future.