Our lab is interested in developing improved anti-angiogenic cancer therapies, as well as understanding the biology of intestinal stem cells. Towards the first interest, we have established increases in hematocrit as well as hepatic erythropoietin production as non-invasive surrogate markers for…
more high-grade inhibition of Vascular Endothelial Growth Factor (VEGF). We are currently investigating the correlation of this erythroid response with optimal anti-tumor response in mice, as well as probing the incidence of this response and correlation with response in human trials of anti-angiogenic agents. Additionally, we are pursuing target validation for novel anti-angiogenic drug targets using knockout and transgenic approaches in mice, and morpholino knockdown in zebrafish. These analyses have implicated a novel receptor as an essential regulator of developmental CNS angiogenesis and a secreted molecule as a potent anti-angiogenic agent. Secondly, we are investigating intestinal stem cell biology. We have established extracellular Wnt signaling as essential for ongoing proliferation in the adult intestine using in vivo expression of the Wnt inhibitor Dkk1. Further, we have successfully developed the first methodology for long-term (>100d) intestinal culture, which notably recapitulates the Wnt-dependency of the intestinal stem cell niche. This system has applications for study of stem cell biology, cancer, tissue engineering and infectious diseases.
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