We are expanding the range of assay techniques that will allow us to understand the sulfation code in chondroitin sulfate glycosaminoglycan (CS-GAG) chains. These assay techniques take advantage of specific chromatography techniques (ion exchange, hydrophilicity) to separate the different disaccharides and monosaccharides that comprise the GAG chains. This is the only technique capable of doing this. We have also initiated mass specrtrophotometric analysis of these separated GAG chains to begin to determine the sequence of sulfations on the different parts of the GAG chain. We have developed assays of growth cone response to chondroitin sulfate proteoglycans. We have completed studies that determined that the activity of myosin II molecular motors are essential for this growth cone turning. Both myosin IIA and IIB appear to be involved in growth cone turning. Modification of their activity by drugs may ultimately prove to be a useful therapeutic approach for treatment of brain injury. Because many of these mechanisms are also found in injury to heart and blood vessels, these approaches may have a more general applicability. We have instituted studies to develop a systems biology approach to CSPG actions. We have identified a number of proteins whose phosphorylation is changed rapidly as neurons are exposed to CSPGs. We have confirmed the changes in several of these with Western blotting techniques. We are now developing an approach to validate changes in the several different signal transduction pathways. We have inititated collaborative studies that have identified the Nogo receptor as a new receptor for CSPGs. In addition our data point to an additional receptor that binds bioactive CSPGs.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
Zip Code
Jin, Jingyu; Tilve, Sharada; Huang, Zhonghai et al. (2018) Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture. Neural Regen Res 13:289-297
Katagiri, Yasuhiro; Morgan, Ashlea A; Yu, Panpan et al. (2018) Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTP?): Implications for proteoglycan signaling. J Biol Chem 293:11639-11647
Yu, Panpan; Pearson, Craig S; Geller, Herbert M (2018) Flexible Roles for Proteoglycan Sulfation and Receptor Signaling. Trends Neurosci 41:47-61
Yi, Mengni; Wei, Tianjiao; Wang, Yanxia et al. (2017) The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke. J Neuroinflammation 14:203
Shumakovich, Marina A; Mencio, Caitlin P; Siglin, Jonathan S et al. (2017) Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells. FASEB J :
Yi, Mengni; Yu, Panpan; Lu, Qin et al. (2016) KCa3.1 constitutes a pharmacological target for astrogliosis associated with Alzheimer's disease. Mol Cell Neurosci 76:21-32
Janecke, Andreas R; Li, Ben; Boehm, Manfred et al. (2016) The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. Am J Med Genet A 170A:103-15
Polackwich, Robert J; Koch, Daniel; McAllister, Ryan et al. (2015) Traction force and tension fluctuations in growing axons. Front Cell Neurosci 9:417
Yu, Panpan; Agbaegbu, Chinyere; Malide, Daniela A et al. (2015) Cooperative interactions of LPPR family members in membrane localization and alteration of cellular morphology. J Cell Sci 128:3210-22
Yu, Zhihua; Yu, Panpan; Chen, Hongzhuan et al. (2014) Targeted inhibition of KCa3.1 attenuates TGF-?-induced reactive astrogliosis through the Smad2/3 signaling pathway. J Neurochem 130:41-49

Showing the most recent 10 out of 25 publications