Woodrow E Lomas

Publications (2)14.62 Total impact

• Source

  Available from: pnas.org

  Article: R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6.

  Minke E Binnerts, Kyung-Ah Kim, Jessica M Bright, Sejal M Patel, Karolyn Tran, Mei Zhou, John M Leung, Yi Liu, Woodrow E Lomas, Melissa Dixon, Sophie A Hazell, Marie Wagle, Wen-Sheng Nie, Nenad Tomasevic, Jason Williams, Xiaoming Zhan, Michael D Levy, Walter D Funk, Arie Abo
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  ABSTRACT: The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.
  Proceedings of the National Academy of Sciences 10/2007; 104(37):14700-5. · 9.68 Impact Factor
• Article: The lymphoid cell surface receptor NTB-A: a novel monoclonal antibody target for leukaemia and lymphoma therapeutics.

  Wouter Korver, Shweta Singh, Shouchun Liu, Xiaoxian Zhao, Shirlee Yonkovich, Allison Sweeney, Kristin Anton, Woodrow E Lomas, Rachel Greenwood, Ashley Smith, [......], Matthew Mueller, Xiaoming Zhan, Elizabeth M Newton, Yi Liu, Jingsong Zhao, Peter Emtage, Michael D Levy, Eric D Hsi, Walter D Funk, Arie Abo
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  ABSTRACT: NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.
  British Journal of Haematology 06/2007; 137(4):307-18. · 4.94 Impact Factor