Our lab aims to systematically identify the structural elements of chondroitin sulfate proteoglycans (CSPGs) that inhibit regeneration following spinal cord injury (SCI). CSPGs are extracellular matrix molecules produced by astrocytes of glial scar tissue following SCI. Central to this project is the use of CSPGs referred to as “Designer PGs,” which contain engineered modifications in the GAG chains and/ or the protein core of the neural CSPG aggrecan. Using established bioassays in vitro, we qualitatively and quantitatively measure growth cone behaviors and morphology as they interact with Designer PG molecules. These measurements are then translated into a composite inhibitory quotient (IQ) score that reflects the inhibitory strength of the particular Designer PG. Scoring is completed through application of our comprehensive inhibitory quotient (IQ) system scoring criteria. The utility of the IQ system is that it allows us to evaluate and directly compare all experimental CSPGs. IQ scores can then be mapped back to the structure of the experimental CSPG, allowing us to pinpoint the inhibitory domains of CSPGs. The long term goal of this methodology is to develop clinical therapies that selectively target the most inhibitory CSPG domains while leaving unaltered the beneficial aspects of the glial scar, thereby supporting regeneration and recovery of function following SCI.

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