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Joining forces with Huntsman Cancer Institute

Quantifying epithelial-mesenchymal transition

PHI is working with scientists at the Huntsman Cancer Institute (HCI) in the battle against cancer. Supported by PHI, Dr. Robert Judson-Torres and his team at HCI aim to develop methods to quantify the phenomena known as epithelial-mesenchymal transition.

HCI is a National Cancer Institute-designated Comprehensive Cancer Center, supported by the National Institutes of Health.

Epithelial-mesenchymal transition (EMT) regulates the deadliest hallmark of cancer — invasion and metastasis. 80% of all cancer forms, including breast, prostate and skin cancer, arise from epithelial cells. Epithelial cells are located throughout the body, lining organs and blood vessels, but also our bodies; the outer layer of our skin are epithelial cells.

Commencement at University of Utah

Commencement at University of Utah

Like normal epithelial cells, cancerous epithelial cells are rigid and immobile, incapable of creating metastasis. To become a lethal colonizer, a cancerous epithelial cell must first transition into a highly plastic and motile mesenchymal cell, hence the term epithelial-mesenchymal transition.

EMT is a physiological transformation caused by a spectrum of different biochemical processes, making the conventional approach of biochemical characterization indirect and adventurous. Contrary to conventional biochemical methods, HoloMonitor’s unique ability to non-invasively quantify physiological traits, such as single-cell plasticity and motility, allows HoloMonitor to directly and more precisely characterize EMT. Moreover, as no reagents contaminate the cells, the same cells may be reused to determine additional cellular characteristics, which is especially useful when working with scarce primary cells extracted from cancer patients.

Insight into metastatic potential provided by real-time quantification of EMT and phenotypic plasticity is conveniently achieved without labels and with single cell resolution.

Dr. Robert Judson-Torres

Robert's research interests focus on the networks of genes and environmental factors that stabilize cell states in adult mammalian organisms, and, conversely, the coordinated sets of destabilizing factors which can lead to tumorigenesis. He is also actively involved with exploring new models of scientific training, communication and publication, including experimenting with forums for post-publication peer review, reproducibility initiatives, and strategies for training the scientific workforce.

Epithelial-mesenchymal transition (EMT) regulates the deadliest hallmark of cancer — invasion and metastasis.

Drawing of EMT and its reverse, mesenchymal-epithelial transition (MET)

Cell images, before (top row) and after EMT (bottom row)

Read more about EMT here: The basics of epithelial-mesenchymal transition, Journal of Clinical Investigation (2009).

Peer Reviewed Articles and Book Chapters

  • Evaluation of Holographic Imaging Cytometer HoloMonitor M4 Motility Applications
    Y. Zhang and R. L. Judson
    Cytometry Part A (2018)

    The HoloMonitor software modules for cell tracking and wound healing analysis were evaluated and compared to the more conventional methods transwell migration and transwell invasion. Both HoloMonitor modules were found to be well-correlated with established standards, yielded reproducible results, and at the same time offered distinct advantages. The wound healing assay was the most tractable and automated method with good reproducibility, while the cell tracking module enabled identification of hypermobile subpopulations.

    Read more
  • Bi-allelic Loss of CDKN2A Initiates Melanoma Invasion via BRN2 Activation
    H. Zeng et al.
    Cancer Cell (2018)

    Utilizing precision genetic engineering and PHI’s HoloMonitor technology, scientists at University of California, San Francisco, have for the first time been able to monitor and map how mutations break down the genetic protection against skin cancer, allowing harmless moles to transform into invasive skin cancer.

    Read more
  • Quantification of mammalian tumor cell state plasticity with digital holographic cytometry
    M Hejna, A Jorapur, Y Zhang, J S Song and R L Judson
    SPIE Conference Proceedings (2018)

    Working with a HoloMonitor M4 digital holographic cytometry platform, we have established a machine learning-based pipeline for high accuracy and label-free classification of adherent cells.

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  • Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi
    I. Yeh et al.
    Nature Communications (2017)

    HoloMonitor was used to measure cell volume. Together with other methods the results identify DPN (deep penetrating nevus) as an intermediate melanocytic neoplasm, with a progression stage positioned between benign nevus and DPN-like melanoma.

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  • High accuracy label-free classification of single-cell kinetic states from holographic cytometry of human melanoma cells
    M. Hejna et al.
    Scientific Reports (2017)

    The authors used singel-cell tracking and machine learning to develop a robust method for label-free classification of adherent cells.

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