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Search: WFRF:(Shires Michael)

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1.
  • Berrout, Jonathan, et al. (author)
  • TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p
  • 2017
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.
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2.
  • Clarke, Emily L., et al. (author)
  • Development of a novel tissue-mimicking color calibration slide for digital microscopy
  • 2018
  • In: Color Research and Application. - : WILEY. - 0361-2317 .- 1520-6378. ; 43:2, s. 184-197
  • Journal article (peer-reviewed)abstract
    • Digital microscopy produces high resolution digital images of pathology slides. Because no acceptable and effective control of color reproduction exists in this domain, there is significant variability in color reproduction of whole slide images. Guidance from international bodies and regulators highlights the need for color standardization. To address this issue, we systematically measured and analyzed the spectra of histopathological stains. This information was used to design a unique color calibration slide utilizing real stains and a tissue-like substrate, which can be stained to produce the same spectral response as tissue. By closely mimicking the colors in stained tissue, our target can provide more accurate color representation than film-based targets, whilst avoiding the known limitations of using actual tissue. The application of the color calibration slide in the clinical setting was assessed by conducting a pilot user-evaluation experiment with promising results. With the imminent integration of digital pathology into the routine work of the diagnostic pathologist, it is hoped that this color calibration slide will help provide a universal color standard for digital microscopy thereby ensuring better and safer healthcare delivery.
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