Browsing by Author "Spruck, Charles"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Image-based assessment of natural killer cell activity against glioblastoma stem cells
    (Wiley, 2024) Du, Yuanning; Metcalfe, Samuel; Akunapuram, Shreya; Ghosh, Sugata; Spruck, Charles; Richardson, Angela M.; Cohen‐Gadol, Aaron A.; Shen, Jia; Neurological Surgery, School of Medicine
    Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.
  • Thumbnail Image
    Item
    SUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma
    (American Society for Clinical Investigation, 2025-03-10) Li, Chunying; Xie, Qiqi; Ghosh, Sugata; Cao, Bihui; Du, Yuanning; Vo, Giau V.; Huang, Timothy Y.; Spruck, Charles; Carpenter, Richard L.; Wang, Y. Alan; Lu, Q. Richard; Nephew, Kenneth P.; Shen, Jia; Biochemistry and Molecular Biology, School of Medicine
    Glioblastoma (GBM) is the most lethal brain cancer, with GBM stem cells (GSCs) driving therapeutic resistance and recurrence. Targeting GSCs offers a promising strategy for preventing tumor relapse and improving outcomes. We identify SUV39H1, a histone-3, lysine-9 methyltransferase, as critical for GSC maintenance and GBM progression. SUV39H1 is upregulated in GBM compared with normal brain tissues, with single-cell RNA-seq showing its expression predominantly in GSCs due to super-enhancer-mediated activation. Knockdown of SUV39H1 in GSCs impaired their proliferation and stemness. Whole-cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq data, we further demonstrated that knockdown of SUV39H1 altered chromatin accessibility in key genes associated with these pathways. Chaetocin, an SUV39H1 inhibitor, mimics the effects of SUV39H1 knockdown, reducing GSC stemness and sensitizing cells to temozolomide, a standard GBM chemotherapy. In a patient-derived xenograft model, targeting SUV39H1 inhibits GSC-driven tumor growth. Clinically, high SUV39H1 expression correlates with poor glioma prognosis, supporting its relevance as a therapeutic target. This study identifies SUV39H1 as a crucial regulator of GSC maintenance and a promising therapeutic target to improve GBM treatment and patient outcomes.