Nurmaa Dashzeveg, PhD
Research Assistant Professor, Pharmacology
Research Program
Cancer-Focused Research
Glycans play a pivotal role in cellular physiology and pathophysiology, yet they remain significantly understudied and inadequately targeted in cancer therapy. Over 50% of proteins undergo glycosylation, and nearly every cell is enveloped in a dense glycan coating. These vital glycan structures serve as the molecular languages for cell-to-cell communication and are critical for immune cell recognition. By fully understanding and harnessing the power of glycans, we have the opportunity to revolutionize cancer treatment, offering new hope and more effective therapies to patients. Our previous research demonstrated that chemotherapy changes glycans increasing formation of circulating tumor cell (CTC) clusters, which have 50-100 times higher metastatic propensity than single CTCs. This metastasis is driven by the inhibition of the terminal sugar residue alpha 2,6-sialic acid (2,6-SA). Deficiency in 2,6-SA, due to the depletion of its' glycosyltransferase ST6Gal1, not only promotes CTC cluster formation and metastatic seeding, but also confers cellular quiescence and resistance to chemo-treatment4. We identified PODXL as a target protein of 2,6-SA/ST6Gal1. Neutralizing PODXL with antibodies inhibits CTC clustering and chemotherapy induced lung metastasis in mice. The glycosylation pattern of PODXL is unique in human pluripotent stem cells and hematopoietic stem cells and cancer cells and cancer-cell-epitope binding anti-PODXL antibody has been developed11. Furthermore, the role of glycans in immune cell recognition and suppression has been reported. For instance, high expression of sialoproteins in cancer cells suppress immune cells through interaction with siglecs (sialic acid binding immunoglobulin-like proteins) and the interaction between PD-1 and PD-L1 is glycan dependent. Collectively, these findings underscore the importance of glycans in cancer progression, therapy resistance, and immune cell suppression. Building on these insights, my research goal is to investigate the role of glycans in cancer cell-immune cell interactions to develop improved immunotherapy and identify liquid biopsy biomarkers predictive for early therapeutic response and cancer progression. Ultimately, these groundbreaking advancement will substantially enhance efficacy of treatment and pave the way for personalized medicine, and enhance patient survival outcomes.