Biology subjects

WEI, B.

Publications and source records attributed to WEI, B..

2 recordsLinked to original sources

bioRxiv2026

High resolution spatial transcriptomics decodes the microenvironmental determinants of response to Nr-CWS therapy in cervical precancerous lesions

Immunotherapy with Nocardia rubra cell wall skeleton (Nr-CWS) can clear human papillomavirus (HPV) and induce regression of cervical precancerous lesions, yet many patients do not respond. The cellular and molecular basis for this heterogeneous clinical outcome remains unknown. Using high-resolution spatial transcriptomics, we profiled squamous intraepithelial lesions (SIL) from patients stratified by their subsequent response to Nr-CWS therapy. We discovered that non-responders were characterized by an immunosuppressive epithelial phenotype, defined by aberrant expression of the pro-inflammatory alarmin S100A9 in squamous epithelial cells (SECs), which was associated with poorer overall survival in cervical cancer. Non-responding lesions were enriched in proliferative (MKI67+) and pro-angiogenic (VEGFA+) SEC subpopulations and spatially organized into a pro-tumorigenic cellular neighborhood (CN-10) overexpressing S100A9 and ANXA1. In contrast, responders exhibited protective glandular-cell-enriched neighborhoods (CN-13) and supportive spatial interactions between lymphatic endothelial cells and fibroblasts. The unfavorable microenvironment was further defined by an immunosuppressive cloak of VCAN+ stromal cells and CD163+ M2 macrophages encircling SECs. Thus, response to Nr-CWS is determined by a pre-existing spatial network of epithelial-stromal-immune interactions, providing a roadmap for patient stratification and rational combination therapies.

cancer biology↗

bioRxiv2020

Identification of sulfenylated cysteines in Arabidopsis thaliana proteins using a disulfide-linked peptide reporter

In proteins, hydrogen peroxide (H2O2) reacts with redox-sensitive cysteines to form cysteine sulfenic acid, also known as S-sulfenylation. These cysteine oxidation events can steer diverse cellular processes by altering protein interactions, trafficking, conformation, and function. Previously, we had identified S-sulfenylated proteins by using a tagged proteinaceous probe based on the yeast AP-1-like (Yap1) transcription factor that specifically reacts with sulfenic acids and traps them through a mixed disulfide bond. However, the identity of the S-sulfenylated amino acid residues remained enigmatic. Here, we present a technological advancement to identify in situ sulfenylated cysteines directly by means of the transgenic Yap1 probe. In Arabidopsis thaliana cells, after an initial affinity purification and a tryptic digestion, we further enriched the mixed disulfide-linked peptides with an antibody targeting the YAP1C-derived peptide (C598SEIWDR) that entails the redox-active cysteine. Subsequent mass spectrometry analysis with pLink 2 identified 1,745 YAP1C cross-linked peptides, indicating sulfenylated cysteines in over 1,000 proteins. Approximately 55% of these YAP1C-linked cysteines had previously been reported as redox-sensitive cysteines (S-sulfenylation, S-nitrosylation, and reversibly oxidized cysteines). The presented methodology provides a noninvasive approach to identify sulfenylated cysteines in any species that can be genetically modified.

plant biology↗