Our work is motivated by a mixture of scientific curiosity and a desire to find solutions to outstanding challenges in tissue regeneration. We pursue challenges in stem cell biology, cell-cell and cell-environment interactions, and biomaterials with a view toward clinical application. Ultimately we seek to discover new methods of bringing about functional tissue regeneration by controlling cells and their environment. Our main research thrusts are:
Applied Progenitor & Stem Cell Biology
The field of stem cell biology is growing rapidly and key findings emerge almost daily. Many of these key findings result in opportunities for direct application to our research questions. This is especially true of new findings with autologous stem and progenitors cells. Most of our work focuses on 3-dimensional (3-D) tissue culture of autologous progenitors and induced pluripotent stem cells (iPSCs). We believe we can accelerate clinical translation by demonstrating our approaches using autologously-derived stem cells cultured in a relevant 3-D geometry. By using autologous cell sources and appropriate 3-D geometries we hope to maintain both biological and clinical relevance and increase the likelihood that new discoveries will quickly translate into therapies.
One aspect of our work under this research area focuses on mesenchymal tissue engineering and its application to repair connective tissues such as bone and cartilage. We are interested in learning how mesenchymal progenitor cells (MSCs) organize and give rise to complex tissues, particularly in the context of a wound environment. We are also interested in how MSCs modulate immune responses that would otherwise compromise healing and regeneration. The discovery of methods to control the proliferation, migration, differentiation, and eventual fate of stem cells in engineered cellular environments is the overarching goal of this thrust area.
Protein Engineering & Biological Interface Design
An essential element of engineering cellular environments is controlling the biological interface. The design of interface materials based on naturally occurring extra-cellular matrix structural polymers and biologically active components provides the foundation for approaches to tackle this important aspect of the cell-environment interaction. In a clinical setting, the outcome of therapies relying on foreign materials typically hinges on interactions at the biological interface. Because of the vast control we can achieve at the molecular level we use protein engineering as a key component of our biological interface design work. By coupling protein engineering with polymer chemistry we have a powerful tool kit with which to control this important interface.
Underlying the design of biological interfaces is the use of 3-dimensional (3-D) tissue culture scaffolds and bulk materials that can support in-vivo remodeling and contribute to tissue regeneration. Biocompatibility, mechanical properties, geometry, and surface characteristics are important considerations in the design of 3-D scaffolds for stem cell culture. The scaffold material properties and 3-D geometry must support the emergence of tissues from sparse seeding conditions and under hostile cellular environments. In this research thrust area we draw heavily from emerging work in biomaterials science and biological engineering to design 3-D scaffolds for specific applications in stem cell biology and regeneration.