Bio

Professional Education


  • Bachelor of Science, University of Auckland (2000)
  • Doctor of Philosophy, University Of Melbourne (2012)
  • Master of Science, University of Auckland (2004)

Stanford Advisors


Publications

Journal Articles


  • Improved quenched fluorescent probe for imaging of cysteine cathepsin activity. Journal of the American Chemical Society Verdoes, M., Oresic Bender, K., Segal, E., van der Linden, W. A., Syed, S., Withana, N. P., Sanman, L. E., Bogyo, M. 2013; 135 (39): 14726-14730

    Abstract

    The cysteine cathepsins are a family of proteases that play important roles in both normal cellular physiology and many human diseases. In cancer, the activity of many of the cysteine cathepsins is upregulated and can be exploited for tumor imaging. Here we present the design and synthesis of a new class of quenched fluorescent activity-based probes (qABPs) containing a phenoxymethyl ketone (PMK) electrophile. These reagents show enhanced in vivo properties and broad reactivity resulting in dramatically improved labeling and tumor imaging properties compared to those of previously reported ABPs.

    View details for DOI 10.1021/ja4056068

    View details for PubMedID 23971698

  • Functional Imaging of Legumain in Cancer Using a New Quenched Activity-Based Probe JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Edgington, L. E., Verdoes, M., Ortega, A., Withana, N. P., Lee, J., Syed, S., Bachmann, M. H., Blum, G., Bogyo, M. 2013; 135 (1): 174-182

    Abstract

    Legumain is a lysosomal cysteine protease whose biological function remains poorly defined. Legumain activity is up-regulated in most human cancers and inflammatory diseases most likely as the result of high expression in populations of activated macrophages. Within the tumor microenvironment, legumain activity is thought to promote tumorigenesis. To obtain a greater understanding of the role of legumain activity during cancer progression and inflammation, we developed an activity-based probe that becomes fluorescent only upon binding active legumain. This probe is highly selective for legumain, even in the context of whole cells and tissues, and is also a more effective label of legumain than previously reported probes. Here we present the synthesis and application of our probe to the analysis of legumain activity in primary macrophages and in two mouse models of cancer. We find that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.

    View details for DOI 10.1021/ja307083b

    View details for Web of Science ID 000313143000036

    View details for PubMedID 23215039

  • Cathepsin B Inhibition Limits Bone Metastasis in Breast Cancer CANCER RESEARCH Withana, N. P., Blum, G., Sameni, M., Slaney, C., Anbalagan, A., Olive, M. B., Bidwell, B. N., Edgington, L., Wang, L., Moin, K., Sloane, B. F., Anderson, R. L., Bogyo, M. S., Parker, B. S. 2012; 72 (5): 1199-1209

    Abstract

    Metastasis to bone is a major cause of morbidity in breast cancer patients, emphasizing the importance of identifying molecular drivers of bone metastasis for new therapeutic targets. The endogenous cysteine cathepsin inhibitor stefin A is a suppressor of breast cancer metastasis to bone that is coexpressed with cathepsin B in bone metastases. In this study, we used the immunocompetent 4T1.2 model of breast cancer which exhibits spontaneous bone metastasis to evaluate the function and therapeutic targeting potential of cathepsin B in this setting of advanced disease. Cathepsin B abundancy in the model mimicked human disease, both at the level of primary tumors and matched spinal metastases. RNA interference-mediated knockdown of cathepsin B in tumor cells reduced collagen I degradation in vitro and bone metastasis in vivo. Similarly, intraperitoneal administration of the highly selective cathepsin B inhibitor CA-074 reduced metastasis in tumor-bearing animals, a reduction that was not reproduced by the broad spectrum cysteine cathepsin inhibitor JPM-OEt. Notably, metastasis suppression by CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth. Together, our findings established a prometastatic role for cathepsin B in distant metastasis and illustrated the therapeutic benefits of its selective inhibition in vivo.

    View details for DOI 10.1158/0008-5472.CAN-11-2759

    View details for Web of Science ID 000300989100019

    View details for PubMedID 22266111

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