Browsing by Author "Furth, Emma E."

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    Inferring super-resolution tissue architecture by integrating spatial transcriptomics with histology
    (Springer Nature, 2024) Zhang, Daiwei; Schroeder, Amelia; Yan, Hanying; Yang, Haochen; Hu, Jian; Lee, Michelle Y. Y.; Cho, Kyung S.; Susztak, Katalin; Xu, George X.; Feldman, Michael D.; Lee, Edward B.; Furth, Emma E.; Wang, Linghua; Li, Mingyao; Pathology and Laboratory Medicine, School of Medicine
    Spatial transcriptomics (ST) has demonstrated enormous potential for generating intricate molecular maps of cells within tissues. Here we present iStar, a method based on hierarchical image feature extraction that integrates ST data and high-resolution histology images to predict spatial gene expression with super-resolution. Our method enhances gene expression resolution to near-single-cell levels in ST and enables gene expression prediction in tissue sections where only histology images are available.
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    Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage
    (American Association for the Advancement of Science, 2023) Soto Ocaña, Joshua; Bayard, Nile U.; Hart, Jessica L.; Thomas, Audrey K.; Furth, Emma E.; Lacy, D. Borden; Aronoff, David M.; Zackular, Joseph P.; Medicine, School of Medicine
    Clostridioides difficile damages the colonic mucosa through the action of two potent exotoxins. Factors shaping C. difficile pathogenesis are incompletely understood but are likely due to the ecological factors in the gastrointestinal ecosystem, mucosal immune responses, and environmental factors. Little is known about the role of pharmaceutical drugs during C. difficile infection (CDI), but recent studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) worsen CDI. The mechanism underlying this phenomenon remains unclear. Here, we show that NSAIDs exacerbate CDI by disrupting colonic epithelial cells (CECs) and sensitizing cells to C. difficile toxin-mediated damage independent of their canonical role of inhibiting cyclooxygenase (COX) enzymes. Notably, we find that NSAIDs and C. difficile toxins target the mitochondria of CECs and enhance C. difficile toxin-mediated damage. Our results demonstrate that NSAIDs exacerbate CDI by synergizing with C. difficile toxins to damage host cell mitochondria. Together, this work highlights a role for NSAIDs in exacerbating microbial infection in the colon.