Browsing by Author "Russell, William K."

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    Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity
    (Cell Press, 2021) Bota-Rabassedas, Neus; Banerjee, Priyam; Niu, Yichi; Cao, Wenjian; Luo, Jiayi; Xi, Yuanxin; Tan, Xiaochao; Sheng, Kuanwei; Ahn, Young-Ho; Lee, Sieun; Parra, Edwin Roger; Rodriguez-Canales, Jaime; Albritton, Jacob; Weiger, Michael; Liu, Xin; Guo, Hou-Fu; Yu, Jiang; Rodriguez, B. Leticia; Firestone, Joshua J.A.; Mino, Barbara; Creighton, Chad J.; Solis, Luisa M.; Villalobos, Pamela; Raso, Maria Gabriela; Sazer, Daniel W.; Gibbons, Don L.; Russell, William K.; Longmore, Gregory D.; Wistuba, Ignacio I.; Wang, Jing; Chapman, Harold A.; Miller, Jordan S.; Zong, Chenghang; Kurie, Jonathan M.
    Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.
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    Microneedle-based sampling of dermal interstitial fluid using a vacuum-assisted skin patch
    (Elsevier, 2024) Jiang, Xue; Wilkirson, Elizabeth C.; Bailey, Aaron O.; Russell, William K.; Lillehoj, Peter B.
    Interstitial fluid (ISF) contains a wealth of biomolecules, yet it is underutilized for diagnostic testing due to a lack of rapid and simple techniques for collecting abundant amounts of fluid. Here, we report a simple and minimally invasive technique for rapidly sampling larger quantities of ISF from human skin. A microneedle array is used to generate micropores in skin from which ISF is extracted using a vacuum-assisted skin patch. Using this technique, an average of 20.8 μL of dermal ISF is collected in 25 min, which is an ∼6-fold improvement over existing sampling methods. Proteomic analysis of collected ISF reveals that it has nearly identical protein composition as blood, and >600 medically relevant biomarkers are identified. Toward this end, we demonstrate the detection of SARS-CoV-2 neutralizing antibodies in ISF collected from COVID-19 vaccinees using two commercial immunoassays, showcasing the utility of this technique for diagnostic testing.