Biology subjects

Chau, T. H.

Publications and source records attributed to Chau, T. H..

5 recordsLinked to original sources

bioRxiv2026

Real-time mass defect-driven prediction of glycopeptide precursors enables enrichment-free serum glycoproteomics

Glycopeptide enrichment remains a cornerstone in glycoproteomics, but bias and reproducibility issues continue to hinder biological insight and clinical translation. Employing curated glycoproteomics datasets and machine learning, we trained a glycopeptide classifier to recognize N-glycopeptide precursors through mass defect signatures. Integration of the classifier into a data-dependent acquisition framework facilitated real-time prediction of N-glycopeptides from human serum and revealed sex differences in murine plasma fucosylation opening avenues for enrichment-free glycoproteomics.

bioinformatics↗

bioRxiv2025

Serum Lewis fucosylation reports on survivorship of patients with septic shock upon admission to intensive care unit

Septic shock, the excessive immune response to pathogen infection, poses a major health concern accounting globally for [~]20% of all deaths. Current methods to establish disease severity are unacceptably slow, unspecific and insensitive, hindering timely and effective treatment. Aiming to identify easy-to-assay glyco-signatures that may identify and guide the clinical management of the most critically unwell patients, we applied quantitative glycomics and glycoproteomics to sera longitudinally collected from septic shock survivors (n=29) and non-survivors (n=8). Glycomics of all 134 serum samples (sampled daily until recovery/death) revealed significant N-glycome dynamics across both patient groups. Unsupervised clustering of the serum N-glycome upon ICU admission (day 1) indicated survivorship-specific glyco- signatures. We therefore employed machine learning to train a random forest model using the serum N-glycome data. The model accurately classified survivorship outcomes of 35 of 37 patients (specificity 94.6%) and correctly predicted 6 of 8 non-survivors (sensitivity 75%) based on ICU day 1 data. Further interrogation of the serum N-glycome data revealed elevated Lewis fucosylation in non-survivors relative to survivors at ICU admission, a finding recapitulated by glycoproteomics. Amongst 58 other serum proteins strongly linked to acute phase response and stress pathways, alpha-1-acid-glycoprotein was identified as a principal carrier of Lewis fucosylation with a potential to stratify septic shock survivors from non- survivors (AUC 0.935). This study lays a foundation for risk stratification of septic shock patients by uncovering easy-to-assay glyco-signatures that identify individuals with poor survival outcomes upon ICU admission, with the potential to translate to early individualised clinical care at the bedside.

biochemistry↗

bioRxiv2024

ST6GAL1-mediated sialyl linkage switching in tumor-associated macrophages drives cancer-promoting nanotubes carrying α2,6-sialylation in anti-inflammatory cells

Tumor-associated macrophages (TAMs) form functionally diverse populations of innate immune cells in the tumor microenvironment (TME). Pro- and anti-inflammatory TAMs are central to cancer progression by shaping inflammation and immune (im)balance, but it remains unknown if polarization-induced remodeling of the TAM glycocalyx critical for cellular communication occurs within the TME. Taking a systems glycobiology approach, we here firstly used cell surface-focused glycomics and lectin flow cytometry of ex vivo polarized monocyte-derived macrophages to demonstrate profound sialyl linkage switching of the surface N-glycome in pro-inflammatory (2,3-sialo-favored) and anti-inflammatory (2,6-sialo-dominant) macrophages. In contrast, no polarization-induced alterations in sialylation were observed in the surface O-glycome. ST6GAL1 that modifies N-glycans with 2,6-sialylation was elevated in anti-inflammatory compared to levels in pro-inflammatory macrophages providing a mechanistic basis for the sialyl linkage switching, which was supported by ST6GAL1 silencing. Interestingly, SNA-focused lectin cytochemistry of anti-inflammatory macrophages revealed dense networks of dynamic 2,6-sialylated protein-based nanotubules forming inter-connecting cellular structures that were absent in pro-inflammatory macrophages. Temporal ST6GAL1 silencing in anti-inflammatory macrophages caused nanotubule disintegration as evidenced by SNA and biotin fluorescence microscopy. Moreover, live cell recordings of anti-inflammatory macrophages cultured with and without colorectal cancer (CRC) cells showed reduced macrophage motility, attenuated inter-macrophage and macrophage-CRC cell interactions and diminished CRC cell proliferation upon ST6GAL1 disruption indicating functional roles of the 2,6-sialylated nanotubules. Finally, sialyl linkage switching was recapitulated in pro- and anti-inflammatory TAMs from tumor tissues of patients with advanced CRC. We report on the mechanistic basis for and functional consequences of glycocalyx remodeling accompanying TAM polarization.

immunology↗

bioRxiv2024

Tumor- and immune-derived N-acetyl-β-D-hexosaminidase drive colorectal cancer and stratify patient risk

Non-invasive prognostic markers are needed to improve survival of colorectal cancer (CRC) patients. Towards this goal, we applied integrative systems glycobiology approaches to tumor tissues and PBMCs from CRC patients and matching controls as well as to a CRC patient-derived cell line. Firstly, quantitative glycomics and glycoproteomics revealed that non-canonical paucimannosidic proteins from monocytic and cancer cell origins are prominent signatures in CRC tumor tissues, and that their expression associates with CRC progression. Guided by these associations, we then showed that N-acetyl-{beta}-D-hexosaminidase (Hex) facilitates paucimannosidic protein biosynthesis in CRC cells and is intimately involved in processes underpinning CRC metastasis (adhesion, migration, invasion, proliferation). Finally, Hex activity was found to be elevated in PBMCs and plasma from patients with advanced CRC relative to matching controls while plasma Hex activity correlated strongly with CRC patient survival. Our study opens avenues for better prognostication, disease risk stratification and therapeutic interventions in CRC. HighlightsO_LI* Non-canonical truncated glycans of immune and cancer origins dominate in CRC tumors C_LIO_LI* N-acetyl-{beta}-D-hexosaminidase, a truncating glycoenzyme, drives tumorigenesis in CRC C_LIO_LI* Activity of plasma N-acetyl-{beta}-D-hexosaminidase stratifies risk in CRC patients C_LI

cancer biology↗

bioRxiv2022

Ultra-sensitive platelet proteome maps the O-glycosylation landscape and charts the response to thrombin dosage

Platelet activation induces the secretion of proteins that promote platelet aggregation and inflammation. However, detailed analysis of the released platelet proteome is hampered by platelets tendency to pre-activate during their isolation and a lack of sensitive protocols for low abundance releasate analysis. Here we detail the most sensitive analysis to date of the platelet releasate proteome with the detection of >1,300 proteins. Unbiased scanning for post-translational modifications within releasate proteins highlighted O-glycosylation as being a major component. For the first time, we detected O-fucosylation on previously uncharacterised sites including multimerin-1 (MMRN1), a major alpha granule protein that supports platelet adhesion to collagen and is a carrier for platelet factor V. The N-terminal EMI domain of MMRN1, a key site for protein-protein interaction, was O-fucosylated at a conserved threonine within a new consensus sequence. Our data suggest that Protein O-fucosyltransferase 1 (POFUT1) is responsible for this modification. Secretion of MMRN1 was reduced in cells lacking POFUT1, supporting a key role of O-fucosylation in MMRN1 function. By comparing releasates from resting and thrombin-treated platelets, 202 proteins were found to be significantly released after high-dose thrombin stimulation. Complementary quantification of the platelet lysates identified >3,800 proteins, which confirmed the platelet origin of releasate proteins by anti-correlation analysis. Low-dose thrombin treatment yielded a smaller subset of significantly regulated proteins with fewer secretory pathway enzymes. The comprehensive platelet proteome resource provided here (larancelab.com/platelet-proteome) allows identification of novel regulatory mechanisms for drug targeting to address platelet dysfunction and thrombosis. Key PointsO_LIHigh-sensitivity proteome mapping of human platelets identifies O-glycosylation of platelet proteins at key functional sites C_LIO_LIPlatelet O-fucosyltransferase POFUT1 regulates the secretion of adhesive protein multimerin-1 (MMRN1) C_LI

biochemistry↗