Research & Scholarship

Current Research and Scholarly Interests


A comparative study of the ethical issues in regards to the laetrile controversy of the 1970s and the experimental stem cell tourism controversy of the 2000s. Starting a new project on comparing international reporting of stem cell research between English speaking regions.

Research Projects


  • A Comparative Study of the Language Used to Describe Laetrile and Stem Cell Therapy: An Evolution in Ethical Problems Through Language (MedScholars Project)
  • Wrinkles in Reporting: Geographical, Political, and Social Dimensions of Print Media Representation of the Stem Cell Research (MedScholars Project)

Publications

Journal Articles


  • Fit to Print? Media Accounts of Unproven Medical Treatments Across Time American Journal of Bioethics: Primary Research Woody Chang, Tracy Caroline Bank, Christopher Scott 2013
  • Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling NATURE MEDICINE Shkreli, M., Sarin, K. Y., Pech, M. F., Papeta, N., Chang, W., Brockman, S. A., Cheung, P., Lee, E., Kuhnert, F., Olson, J. L., Kuo, C. J., Gharavi, A. G., D'Agati, V. D., Artandi, S. E. 2012; 18 (1): 111-119

    Abstract

    Mechanisms of epithelial cell renewal remain poorly understood in the mammalian kidney, particularly in the glomerulus, a site of cellular damage in chronic kidney disease. Within the glomerulus, podocytes--differentiated epithelial cells crucial for filtration--are thought to lack substantial capacity for regeneration. Here we show that podocytes rapidly lose differentiation markers and enter the cell cycle in adult mice in which the telomerase protein component TERT is conditionally expressed. Transgenic TERT expression in mice induces marked upregulation of Wnt signaling and disrupts glomerular structure, resulting in a collapsing glomerulopathy resembling those in human disease, including HIV-associated nephropathy (HIVAN). Human and mouse HIVAN kidneys show increased expression of TERT and activation of Wnt signaling, indicating that these are general features of collapsing glomerulopathies. Silencing transgenic TERT expression or inhibiting Wnt signaling through systemic expression of the Wnt inhibitor Dkk1 in either TERT transgenic mice or in a mouse model of HIVAN results in marked normalization of podocytes, including rapid cell-cycle exit, re-expression of differentiation markers and improved filtration barrier function. These data reveal an unexpected capacity of podocytes to reversibly enter the cell cycle, suggest that podocyte renewal may contribute to glomerular homeostasis and implicate the telomerase and Wnt-β-catenin pathways in podocyte proliferation and disease.

    View details for DOI 10.1038/nm.2550

    View details for Web of Science ID 000299018600036

  • Telomerase modulates Wnt signalling by association with target gene chromatin NATURE Park, J., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., McLaughlin, M., Veenstra, T. D., Nusse, R., McCrea, P. D., Artandi, S. E. 2009; 460 (7251): 66-U77

    Abstract

    Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.

    View details for DOI 10.1038/nature08137

    View details for Web of Science ID 000267545200030

    View details for PubMedID 19571879

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