A major focus of our lab is the repair of spinal cord injury (SCI), for which there are no treatments available that can achieve regeneration. Development of clinically effective strategies to restore function after SCI will require consideration of multiple aspects of this inhibitory environment. Ultimately, we aim to develop a combinatorial therapy that addresses multiple barriers to spinal cord repair by incorporating substrate-immobilized biochemical cues, genetically encoded regulatory factors, and cell replacement.
This array technique is based on a library of lentiviral reporters of transcription factor activation that drive expression of luciferase. Extracellular cues initiate complex intracellular signaling cascades that terminate in translocation of multiple transcription factors to the nucleus to directly modulate gene expression. Bioluminescence imaging is then performed in live, 3D cultures to quantitatively monitor transcription factor activation in real-time, which represents the current "functional state" of a cell and ultimately drives differentiation.
The extracellular environment has significant, but largely uncharacterized, involvement in function of the central nervous system. Biomaterials can be engineered to present defined microenvironments that can greatly simplify the experimental variability in biological systems so that effects of a single variable can be experimentally isolated in vitro. In addition, through systematic manipulation of different microenvironmental features presented by the biomaterial, we can identify which aspects of a cell's surroundings instrumentally contribute to specific pathologies and apply this knowledge to develop new clinical therapies that act by locally altering the extracellular environment. In particular, we aim to use biomaterial tools to identify key physiological interactions between cells and their environment during central nervous system tissue development, repair, and disease progression. Identification of crucial alterations in these interactions will lead to impactful mechanistic discoveries and ultimately new clinical strategies based on controlled manipulation of these interactions.