Decoding the Sugar Code: Understanding the Function of Glycans in Health and Disease

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biochemistry and Molecular Biology".

Deadline for manuscript submissions: 15 January 2027 | Viewed by 829

Special Issue Editors


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Laboratório de Biologia Celular de Glicoconjugados, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Interests: immunology; infectious disease; parasite–host interaction; leishmania; Trypanosoma cruzi; glycobiology; glycoconjugates; glycosyltransferases; glycoproteins
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Laboratório de Biologia Celular de Glicoconjugados, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Interests: glycolipids; physiological conditions; pathological conditions
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1. Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21045-900, RJ, Brazil
2. Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Interests: glycoimmunology of infectious diseases
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Campus Duque de Caxias Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 25.240-005, RJ, Brazil
Interests: drug resistance in cancer; immunity; infection; parasite–host interaction

Special Issue Information

Dear Colleagues, 

Glycobiology is an expanding and dynamic field dedicated to understanding the structures, functions, and biological significance of glycoconjugates, including glycoproteins, glycolipids, and complex glycans. Over the past few decades, remarkable advances have demonstrated that glycans are not merely structural components but key regulators of diverse physiological and pathological processes. They participate in immune modulation, protein–protein and protein–carbohydrate interactions, cell signaling pathways, metabolic regulation, cancer progression, and host–pathogen interactions, among many other biological events. 

Driven by rapid technological progress in glycomics, glycoproteomics, and advanced analytical techniques, the study of glycan structures and functions has become central to both basic and translational research. These advances have enabled the identification of novel biomarkers, therapeutic targets, and mechanisms that underlie health and disease. 

In this Special Issue, we welcome contributions that explore new findings, methodologies, and conceptual advances related to glycobiology. Studies addressing how glycans and glycoconjugates regulate molecular mechanisms and influence physiological homeostasis or disease development are particularly encouraged. We also invite interdisciplinary research spanning immunology, oncology, infectious diseases, neuroscience, and metabolism, reflecting the broad and impactful roles of glycans across biological systems.

Dr. Leonardo Freire-de-Lima
Dr. Leonardo Marques Da Fonseca
Dr. Célio Geraldo Freire-de-Lima
Dr. Alexandre Morrot
Dr. Raphael do Carmo Valente
Guest Editors

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Keywords

  • glycobiology
  • glycoproteins
  • glycolipids
  • glycosyltransferases
  • glycoconjugates
  • glycosylation
  • glycomics
  • health and disease
  • molecular mechanisms
  • biological functions

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Published Papers (1 paper)

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Research

18 pages, 4444 KB  
Article
The Colorectal Cancer Glycocode: Tumour Sialylation Is Associated with an Immune-Excluded Phenotype and Distinct Therapeutic Signatures
by Abdulaziz Alfahed, Glowi Alasiri and Abdulrahman A. Alahmari
Biology 2026, 15(9), 705; https://doi.org/10.3390/biology15090705 - 30 Apr 2026
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Abstract
Background: Tumour glycosylation regulates immune modulation and progression, but whether the CRC sialylome—the complete repertoire of sialylated glycans—defines a biologically distinct subtype remains unclear. We investigated how the “sugar code” shapes CRC biology, immunity, and therapeutic response. Methods: Transcriptomic data from three CRC [...] Read more.
Background: Tumour glycosylation regulates immune modulation and progression, but whether the CRC sialylome—the complete repertoire of sialylated glycans—defines a biologically distinct subtype remains unclear. We investigated how the “sugar code” shapes CRC biology, immunity, and therapeutic response. Methods: Transcriptomic data from three CRC cohorts (TCGA, Sidra-LUMC, and CPTAC-2; n = 988) were batch-corrected and integrated. Single-sample gene set enrichment analysis (ssGSEA) quantified sialyltransferase expression, sialic acid metabolism, EMT, MDR mechanisms, immune phenotypes, and Siglec-associated transcriptional signatures. GSEA, gene ontology enrichment analysis (GOEA), and drug ontology enrichment analysis (DOEA) characterised pathways and identified drug response-associated transcriptional signatures. Results: High sialylome activity defined a genomically stable but clinically advanced CRC subset enriched for left-sided tumours, mucinous histology, MSI, and BRAF mutations. At the transcriptional level, Sialyl-High tumours were associated with a mesenchymal, stromal-remodelling programme accompanied by reduced proliferative activity. They demonstrated enrichment of vesicular trafficking-related pathways alongside reduced representation of canonical efflux-associated programmes. Critically, the sialylome was associated with Siglec-related immune signatures, with sialylated glycan-related gene expression correlating with Siglec receptor expression (CD33 and SIGLEC7/9/10), consistent with an immune-inflamed yet structurally excluded microenvironment. DOEA identified selective enrichment of drug-response signatures related to sialic acid metabolism inhibitors (oseltamivir and Neu5Ac) and glycocalyx-disrupting agents (ginsenosides and soyasaponins). Conclusions: The CRC sialylome is associated with tumour phenotypic variation, including immune-excluded states linked to Siglec-associated transcriptional signatures and patterns consistent with non-canonical drug resistance programmes. These findings position the “sugar code” as a central organising principle in CRC and identify glycan-directed therapies as a promising strategy for the targeting of this aggressive subtype. Full article
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