The characterization of aberrant glycosylation patterns in biopsied patient samples represents a remarkable challenge for scientists and medical doctors due to the lack of specific methods for their detection. Here, we report the development of a histological method, dubbed CHoMP—Chemoenzymatic Histology of Membrane Polysaccharides—for analyzing glycosylation patterns in mammalian tissues. This method exploits a recombinant glycosyltransferase to transfer a monosaccharide analog equipped with a chemical handle to a specific cell-surface glycan target, which can then be derivatized with imaging probes using bioorthogonal click chemistry for visualization. We applied CHoMP to survey changes in expression of N-acetyllactosamine (LacNAc) in human samples from patients afflicted with lung adenocarcinoma and observed a sharp decrease in expression levels between normal and early grade tumors, suggestion a potential application of this technique in early cancer diagnosis.

Glycans anchored on cell-surface receptors are active modulators of receptor signaling. A strategy is presented that enforces transient changes to cell-surface glycosylation patterns to tune receptor signaling. This approach, termed in situ glycan editing, exploits recombinant glycosyltransferases to incorporate monosaccharides with linkage specificity onto receptors in situ. α2,3-linked sialic acid or α1,3-linked fucose added in situ suppresses signaling through epidermal growth factor receptor and fibroblast growth factor receptor. We also applied the same strategy to regulate the electrical signaling of a potassium ion channel–human ether-à-go-go-related gene channel. Compared to gene editing, no long-term perturbations are introduced to the treated cells. In situ glycan editing therefore offers a promising approach for studying the dynamic role of specific glycans in membrane receptor signaling and ion channel functions.

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