CAREER: Engineering instructive niches to precisely guide single stem cells

About This Grant

Stem cells have the ability to develop into different types of cells. These cells are necessary to build and maintain normal tissues. However, damaged tissues often do not heal themselves. This Faculty Early Career Development Program (CAREER) project will pioneer new approaches to understand how stem cells can be precisely guided to regenerate tissues by building instructive niches (microenvironments) around them, one cell at a time. The approach developed can potentially be integrated with other existing biomanufacturing approaches to fabricate new tissues by providing gel-coated cells with locally defined properties as building blocks. The educational program will provide both high school teachers and students from diverse backgrounds with opportunities to be engaged in hands-on research activities that integrate multiple fields in science, technology, engineering and math (STEM). This integrated effort is designed to promote early exposure to multidisciplinary thinking and learning processes that are critical to solve challenging problems in biological systems. The investigator's career goal is to achieve a paradigm shift by showing that microgels can be designed as instructive cues to precisely understand and control single stem cell functions. Toward this goal, this CAREER project is based on the central premise that building instructive niches that recapitulate physiologically relevant extracellular matrix properties around single cells offers a unique direction that will enable investigations into how microenvironments regulate stem cell functions at an unprecedented resolution. To confirm this premise, the project will investigate how three-dimensional microenvironments can be designed to precisely direct fundamental processes that are essential for cell fate decision, including cell growth, symmetry breaking, asymmetric division and differentiation at the single cell level. Multidisciplinary approaches will be employed to pursue this project, including biomaterial design, droplet microfluidics, biophysical methods, mathematical modeling, imaging and genetic engineering. The research will yield a library of designed microenvironment models that can be used to recapitulate and control specific biological processes of cell fate decision in a deterministic manner. A greater understanding of cell fate decision enabled by the tools developed in this research will aid in endeavors to develop effective stem cell-based therapies and biomanufacturing approaches for tissue regeneration. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.