GlyCORE: Glycoscience Center of Research Excellence

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Project Summary Understanding tissue healing and protein expression after injury is crucial in regenerative medicine. The glycoprotein CTHRC1 plays a vital role in tissue repair, regulation of fat cell formation, and bone development. It is produced by activated fibroblasts and contributes to metabolic efficiency and the survival of endothelial cells, which maintain homeostasis and capillary networks during healing. However, abnormal CTHRC1 expression is observed in chronic inflammation as well as malignant growth. While glycosylation is essential for the proper functioning of many secreted proteins, we don't yet understand how glycosylation impacts the beneficial effects of CTHRC1. CTHRC1 is a secreted protein with a 16-amino acid pro-peptide at its N-terminus. Removing this pro-peptide increases the biological activity of the protein. Our recent findings indicate that both the full-length and truncated forms of CTHRC1 promote glycolysis in endothelial cells, with the truncated form being particularly potent. Even though these initial structure–activity observations highlight the importance of protein modifications in controlling activity of CTHRC1, no further studies exploring the relationship between structure and function of CTHRC1 have been conducted. Additionally, the specific receptor for CTHRC1 remains unknown. In this collaborative project, our goal is to investigate how glycosylation of CTHRC1 influences its binding to target cells and its role in regulating energy metabolism. We will also track the cellular localization of internalized CTHRC1 by chemically tagging different amino acid residues to elucidate its site of action. Understanding the pro-glycolytic effects of CTHRC1 is instrumental in comprehending the functioning of endothelial cells during ongoing tissue repair. This proposal aims to develop CTHRC1 into a valuable tool to better understand the characteristics of activated endothelial cells during wound healing. To accomplish this objective, we will adopt an interdisciplinary team-science approach that builds upon the expertise and resources of the Centers for Biomedical Research Excellence (COBRE) supported by NIGMS in Mississippi and Maine. By leveraging state-of-the-art glycoscience techniques, we aim to address the challenges faced in the field of regenerative medicine.