STIMULI-RESPONSIVE POLYMERIC NANOPARTICLES AS TOOLS FOR PROBING NEURODEGENERATION IN SITU funding sources: SC EPSCoR/IDeA, SC INBRE DRP Current techniques of neurodegenerative disease detection involve lysing cell populations or analyzing post-mortem tissue; these techniques create a significant bottleneck in obtaining information about cellular characteristics of neurodegeneration because they do not adequately preserve information on disease progression. Evidence from multiple neurodegenerative disorders demonstrates that lysosomal hydrolase activities become upregulated as a homeostatic mechanism at late stages of disease, suggesting correlation between activity and disease progression. Although, all neurodegenerative disorders involve lysosomal dysfunction and storage products, the pathway by which accumulation leads to neurodegeneration can vary patient to patient. Therefore, there is a critical need to perform mechanistic studies into the temporospatial behavior of neurodegenerative pathways in live cells, with the goal of correlating known cellular changes in neurodegeneration to identifiable and measurable increases in lysosomal hydrolase activity in real time to allow for personalized disease analysis. Biologically interactive, biohybrid nanoparticles are a unique tool with the potential to probe known intracellular behaviors of autophagosomal-lysosomal fusion, mitochondrial dysfunction, and neuroinflammation in situ, by responding directly to the pathogenesis of disease. Biohybrid nanoparticles, composed of amphiphilic polymers and enzymatic substrates, with varying degrees of hydrophobicity, will be created to infiltrate cells and release a monitorable signal when in contact with an upregulated lysosomal hydrolase. Therefore, nanoparticles will be both stimuli-responsive and biologically interactive.
CONTACT email larsenj at clemson . edu phone 864.656.2621 office 130 Earle Hall
Bipin Paruchuri
Zoe McNelis
related presentations 1. Smith, S.; Larsen. J. M. “Correlating Homeostatic Lysosomal Enzyme Upregulation with Autophagic Neurodegenerative Disease Behavior.” Clemson Student Research Forum, Clemson, SC (April 4, 2018). 2. Smith, S.; Larsen J.M. “Probing differences in Autophagic Behavior in GM1 Gangliosidosis Felines Compared to Normal Controls.” Clemson University Undergraduate Research Symposium. Clemson, SC. (July 2018). 3. Smith, S.; Larsen, J.M. “Correlating Autophagic Behavior to Lysosomal Hydrolase Upregulation for Diagnostics in Lysosomal Storage Disease.” Biomedical Engineering Society Annual Meeting. Atlanta, GA. (October 2018). 4. Paruchuri, B.; Larsen, J. "Biohybrid polymersome-mediated enzyme replacement therapy for GM1 Gangliosidosis", Graduate Research and Discovery Symposium, Clemson University, April 3-4, 2019 5. Smith, S.; Champion, C.; Larsen, J. “Correlating Lysosomal Enzyme Upregulation with Neurodegenerative Disease Pathology.” Clemson Student Research Forum, Clemson University, April 5, 2019. 6. Paruchuri, B.; Larsen, J. “Biohybrid polymersome-mediated enzyme replacement therapy for GM1 Gangliosidosis”, Chemical and Biomolecular Engineering Graduate Research Symposium, Madren Center, Clemson, April 9, 2019 7. Smith, S.; Larsen, J. Probing GM1 Gangliosidosis to Determine a Biomarker for Neurodegeneration. 2019 SC EPSCoR State Conference, Greenville SC, April 12, 2019. 8. Bell, J.; Larsen, J. Loading NHS-PEG2000-NHS PEG-b-PLA Apolipoprotein E Nanoparticles with Beta-Galactosidase Bovine. Undergraduate Poster Symposium, Clemson University, Clemson SC, July 25, 2019.