MBI Publications

MBI Publications for Wing Cheong (Jon) Lo (5)

  • W. Lo, L. Chen, M. Wang and Q. Nie
    A Efficient and Robust Method for Steady State Patterns in Reaction-Diffusion Systems
    Journal of Computational Physics (2012) (In Press)

    Abstract

  • W. Lo, S. Zhou, A. Lander and Q. Nie
    Robust and Precise Morphogen-mediated Patterning: Tradeoffs, Constraints and Mechanisms.
    (2012) (Submitted)

    Abstract

  • S. Zhou, W. Lo, J. Suhalim, M. Digman, E. Gratton, Q. Nie and A. Lander
    Free Extracellular Diffusion Creates the Dpp Morphogen Gradient of the Drosophila Wing Disc
    Current Biology (2012) (In Press)

    Abstract

  • E. Martin, A. Friedman and W. Lo
    Mathematical Model of Colitis-associated Colon Cancer
    Journal of Theoretical BiologyVol. 317 (2013) pp. 2. 20-29

    Abstract

    As a result of chronic inflammation of their colon, patients with ulcerative colitis or Crohn's disease are at risk of developing colon cancer. In this paper, we consider the progression of colitis-associated colon cancer. Unlike normal colon mucosa, the inflammed colon mucosa undergoes genetic mutations, affecting, in particular, tumor suppressors TP53 and adenomatous polyposis coli (APC) gene. We develop a mathematical model that involves these genes, under chronic inflammation, as well as NF-?ºB, ?²-catenin, MUC1 and MUC2. The model demonstrates that increased level of cells with TP53 mutations results in abnormal growth and proliferation of the epithelium; further increase in the epithelium proliferation results from additional APC mutations. The model may serve as a conceptual framework for further data-based study of the early stage of colon cancer.
  • H. Park, C. Chou and W. Lo
    Polarization of Diploid Daughter Cells Directed by Spatial Cues and GTP Hydrolysis of Cdc42 in Budding Yeast.
    PLoS ONEVol. 8 No. 2 (2013)

    Abstract

    Cell polarization occurs along a single axis that is generally determined by a spatial cue. Cells of the budding yeast exhibit a characteristic pattern of budding, which depends on cell-type-specific cortical markers, reflecting a genetic programming for the site of cell polarization. The Cdc42 GTPase plays a key role in cell polarization in various cell types. Although previous studies in budding yeast suggested positive feedback loops whereby Cdc42 becomes polarized, these mechanisms do not include spatial cues, neglecting the normal patterns of budding. Here we combine live-cell imaging and mathematical modeling to understand how diploid daughter cells establish polarity preferentially at the pole distal to the previous division site. Live-cell imaging shows that daughter cells of diploids exhibit dynamic polarization of Cdc42-GTP, which localizes to the bud tip until the M phase, to the division site at cytokinesis, and then to the distal pole in the next G1 phase. The strong bias toward distal budding of daughter cells requires the distal-pole tag Bud8 and Rga1, a GTPase activating protein for Cdc42, which inhibits budding at the cytokinesis site. Unexpectedly, we also find that over 50% of daughter cells lacking Rga1 exhibit persistent Cdc42-GTP polarization at the bud tip and the distal pole, revealing an additional role of Rga1 in spatiotemporal regulation of Cdc42 and thus in the pattern of polarized growth. Mathematical modeling indeed reveals robust Cdc42-GTP clustering at the distal pole in diploid daughter cells despite random perturbation of the landmark cues. Moreover, modeling predicts different dynamics of Cdc42-GTP polarization when the landmark level and the initial level of Cdc42-GTP at the division site are perturbed by noise added in the model.

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