Glycobiology & Glycotherapeutics

Defining Clinically Relevant Protein-Glycan Interactions

Glycans are complex biomolecules made from sugars and play a critical role in nearly all aspects of biology. Glycans are located on the surfaces of cells and provide cells with the ability to recognize and interact with each other. The expression of carbohydrates helps our immune system to identify viruses and bacteria, determine whether cells are healthy or diseased, and dictates the manner in which the immune system processes these cells, responds to injury, and mediates tissue repair. Glycans are recognized by direct interactions with proteins, often in the context of distinct neighboring peptide motifs. While many drugs target proteins to treat disease, glycans and glycan-protein interactions represent a unique and large class of druggable targets that could be used to develop new treatments. We are developing tools to study the roles of glycan-protein interactions in innate immunity, thrombosis, and cancer and identifying molecules that target these interactions as therapeutic agents.

Team Members

  • Bibek Dhakal, Ph.D.

  • Ashley DeJong, Ph.D.

  • Samira Escopy, Ph.D.

  • Carolyn Haller, Ph.D.

  • Geeta Karki, Ph.D.

  • Kaicheng Li, Ph.D.

  • Diane Park, Ph.D.

Relevant Publications

  • Wong DJ, Park DD, Park SS, Haller CA, Chen J, Dai E, Liu L, Mandhapati AR, Eradi P, Dhakal B, Wever WJ, Hanes M, Sun L, Cummings RD, Chaikof EL. A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis. Blood 2021;138:1182–93. https://doi.org/10.1182/blood.2020009428

  • Park DD, Chen J, Kudelka MR, Jia N, Haller CA, Kosaraju R, Premji AM, Galizzi M, Nairn AV, Moremen KW, Cummings RD, Chaikof EL. Resident and elicited murine macrophages differ in expression of their glycomes and glycan-binding proteins. Cell Chem Biol 2021;28:567-582.e4. https://doi.org/10.1016/j.chembiol.2020.12.005

  • Matsumoto Y, Kudelka MR, Hanes MS, Lehoux S, Dutta S, Jones MB, Stackhouse KA, Cervoni GE, Heimburg-Molinaro J, Smith DF, Ju T, Chaikof EL, Cummings RD. Erratum to: Identification of Tn antigen O-GalNAc-expressing glycoproteins in human carcinomas using novel anti-Tn recombinant antibodies. Glycobiology 2020;30:1015. https://doi.org/10.1093/glycob/cwaa044

  • Sardar MYR, Mandhapati AR, Park S, Wever WJ, Cummings RD, Chaikof EL. Convergent Synthesis of Sialyl LewisX- O-Core-1 Threonine. J Org Chem 2018;83:4963–72. https://doi.org/10.1021/acs.joc.7b03117

  • Patel MS, Miranda-Nieves D, Chen J, Haller CA, Chaikof EL. Targeting P-selectin glycoprotein ligand-1/P-selectin interactions as a novel therapy for metabolic syndrome. Transl Res 2017;183:1–13. https://doi.org/10.1016/j.trsl.2016.11.007

  • Krishnamurthy VR, Sardar MYR, Ying Y, Song X, Haller C, Dai E, Wang X, Hanjaya-Putra D, Sun L, Morikis V, Simon SI, Woods RJ, Cummings RD, Chaikof EL. Glycopeptide analogues of PSGL-1 inhibit P-selectin in vitro and in vivo. Nat Commun 2015;6:6387. https://doi.org/10.1038/ncomms7387