Molecular elucidation and engineering of stem cell fate decisions

Stem cells play critical roles in the development of organisms, as well as in the maintenance and repair of organs and tissues throughout adulthood.  Advancing our understanding of mechanisms that control stem cell behavior – in particular their two hallmark properties of self-renewal and differentiation into specialized cells – will enable these cells to be increasingly harnessed to repair tissues damaged by disease or injury.  Stem cells reside within specialized microenvironments or niches that present them with a spectrum of regulatory signals to control their behavior. In particular, the niche presents stem cells with a range of molecular cues, and it has also been become increasingly apparent that key biophysical features of the environment modulate the presentation of this biochemical information. For example, spatial and temporal variation in the presentation of cues is important information that can impact fate decisions and tissue structure. In addition, the tissue matrix can have variable bulk mechanical properties and surface topographical properties depending on how its assembled.
 
We have created several technology platforms to investigate these problems, and in particular to understand and control the differentiation of adult neural stem cells and human pluripotent stem cells into neurons. First, we are developing and harnessing optogenetics as a system to investigate how cellular signaling dynamics impact fate decisions. Second, we develop bioactive, synthetic material systems to investigate the effects of cell-matrix and cell-cell interactions on cellular function. Finally, we work towards translating the basic information that emerges from both of these efforts into safe, scaleable, fully defined, robust culture and implantation systems for stem cell based regenerative medicine efforts to treat human disease.