Stanford Advisors


  • Li Wang, Postdoctoral Faculty Sponsor

All Publications


  • Archaeal G-quadruplexes: a novel model for understanding unusual DNA/RNA structures across the tree of life NUCLEIC ACIDS RESEARCH Aktary, Z., Sorg, K., Cucchiarini, A., Vesco, G., Noury, D., Zhang, R., Jourdain, T., Verga, D., Mahou, P., Olivier, N., Bohalova, N., Porubiakova, O., Brazda, V., Bouvier, M., Kwapisz, M., Clouet-d'Orval, B., Allers, T., Lestini, R., Mergny, J., Guittat, L. 2026; 54 (4)

    Abstract

    Archaea, a domain of microorganisms found in diverse environments, including the human microbiome, represent the closest known prokaryotic relatives of eukaryotes. This phylogenetic proximity positions them as a relevant model for investigating the evolutionary origins of nucleic acid secondary structures such as G-quadruplexes (G4s) which play regulatory roles in transcription and replication. Although G4s have been extensively studied in eukaryotes, their presence and function in archaea remain poorly characterized. In this study, a genome-wide analysis of the halophilic archaeon Haloferax volcanii identified over 5800 potential G4-forming sequences. Biophysical validation confirmed that many of these sequences adopt stable G4 conformations in vitro. Using G4-specific detection tools and super-resolution microscopy, G4 structures were visualized in vivo in both DNA and RNA across multiple growth phases. Comparable findings were observed in the thermophilic archaeon Thermococcus barophilus. Functional analysis using helicase-deficient H. volcanii strains further identified candidate enzymes involved in G4 resolution. These results establish H. volcanii as a tractable archaeal model for G4 biology.

    View details for DOI 10.1093/nar/gkag067

    View details for Web of Science ID 001680170800001

    View details for PubMedID 41641698

    View details for PubMedCentralID PMC12873603

  • G-quadruplex structures as modulators of alternative promoter usage NAR GENOMICS AND BIOINFORMATICS Zhang, R., Mergny, J. 2025; 7 (4): lqaf208

    Abstract

    The precise regulation of gene transcription relies on promoters, and the selection of specific promoters for a particular gene is a key determinant of transcript diversity. However, the regulatory mechanisms governing promoter selection are not fully understood. G-quadruplexes (G4s) are unique DNA noncanonical secondary structures that have emerged as important regulators of gene expression. In this study, we systematically analyzed the relationship between G4 structures and alternative promoters (APs) in two cancer cell lines, K562 and HepG2, by integrating native elongating transcript-cap analysis of gene expression and G4 ChIP-seq datasets. We identified 573 differentially utilized APs (|fold change| > 2, false discovery rate < 0.05), 26% of which being associated with G4 structures within 100 base pairs. Notably, G4-associated promoters predominantly exhibited increased activity, suggesting that G4s generally promote AP selection. Furthermore, treatment with G4 ligands induced the generation of APs, suggesting that the stabilization of G4 structures may modulate AP usage. Collectively, these findings provide new insights into the G4-based mechanisms that regulate transcript isoform diversity.

    View details for DOI 10.1093/nargab/lqaf208

    View details for Web of Science ID 001651772800001

    View details for PubMedID 41480590

    View details for PubMedCentralID PMC12754776

  • Multi-View Radiomics Feature Fusion Reveals Distinct Immuno-Oncological Characteristics and Clinical Prognoses in Hepatocellular Carcinoma CANCERS Gu, Y., Huang, H., Tong, Q., Cao, M., Ming, W., Zhang, R., Zhu, W., Wang, Y., Sun, X. 2023; 15 (8)

    Abstract

    Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, and the pronounced intra- and inter-tumor heterogeneity restricts clinical benefits. Dissecting molecular heterogeneity in HCC is commonly explored by endoscopic biopsy or surgical forceps, but invasive tissue sampling and possible complications limit the broadeer adoption. The radiomics framework is a promising non-invasive strategy for tumor heterogeneity decoding, and the linkage between radiomics and immuno-oncological characteristics is worth further in-depth study. In this study, we extracted multi-view imaging features from contrast-enhanced CT (CE-CT) scans of HCC patients, followed by developing a fused imaging feature subtyping (FIFS) model to identify two distinct radiomics subtypes. We observed two subtypes of patients with distinct texture-dominated radiomics profiles and prognostic outcomes, and the radiomics subtype identified by FIFS model was an independent prognostic factor. The heterogeneity was mainly attributed to inflammatory pathway activity and the tumor immune microenvironment. The predominant radiogenomics association was identified between texture-related features and immune-related pathways by integrating network analysis, and was validated in two independent cohorts. Collectively, this work described the close connections between multi-view radiomics features and immuno-oncological characteristics in HCC, and our integrative radiogenomics analysis strategy may provide clues to non-invasive inflammation-based risk stratification.

    View details for DOI 10.3390/cancers15082338

    View details for Web of Science ID 000977075700001

    View details for PubMedID 37190266

    View details for PubMedCentralID PMC10137067