Bio

Professional Education


  • Doctor of Philosophy, University of Toronto (2010)

Stanford Advisors


Publications

Journal Articles


  • PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2 SCIENCE TRANSLATIONAL MEDICINE Taniguchi, C. M., Miao, Y. R., Diep, A. N., Wu, C., Rankin, E. B., Atwood, T. F., Xing, L., Giaccia, A. J. 2014; 6 (236)
  • Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes. Nature medicine Taniguchi, C. M., Finger, E. C., Krieg, A. J., Wu, C., Diep, A. N., Lagory, E. L., Wei, K., McGinnis, L. M., Yuan, J., Kuo, C. J., Giaccia, A. J. 2013; 19 (10): 1325-1330

    Abstract

    Signaling initiated by hypoxia and insulin powerfully alters cellular metabolism. The protein stability of hypoxia-inducible factor-1 alpha (Hif-1?) and Hif-2? is regulated by three prolyl hydroxylase domain-containing protein isoforms (Phd1, Phd2 and Phd3). Insulin receptor substrate-2 (Irs2) is a critical mediator of the anabolic effects of insulin, and its decreased expression contributes to the pathophysiology of insulin resistance and diabetes. Although Hif regulates many metabolic pathways, it is unknown whether the Phd proteins regulate glucose and lipid metabolism in the liver. Here, we show that acute deletion of hepatic Phd3, also known as Egln3, improves insulin sensitivity and ameliorates diabetes by specifically stabilizing Hif-2?, which then increases Irs2 transcription and insulin-stimulated Akt activation. Hif-2? and Irs2 are both necessary for the improved insulin sensitivity, as knockdown of either molecule abrogates the beneficial effects of Phd3 knockout on glucose tolerance and insulin-stimulated Akt phosphorylation. Augmenting levels of Hif-2? through various combinations of Phd gene knockouts did not further improve hepatic metabolism and only added toxicity. Thus, isoform-specific inhibition of Phd3 could be exploited to treat type 2 diabetes without the toxicity that could occur with chronic inhibition of multiple Phd isoforms.

    View details for DOI 10.1038/nm.3294

    View details for PubMedID 24037093

  • Blood and bones Osteoblastic HIF signaling regulates erythropoiesis CELL CYCLE Wu, C., Rankin, E. B., Giaccia, A. J. 2012; 11 (12): 2221-2222

    View details for DOI 10.4161/cc.20635

    View details for Web of Science ID 000305353000003

    View details for PubMedID 22627672

  • The HIF Signaling Pathway in Osteoblasts Directly Modulates Erythropoiesis through the Production of EPO CELL Rankin, E. B., Wu, C., Khatri, R., Wilson, T. L., Andersen, R., Araldi, E., Rankin, A. L., Yuan, J., Kuo, C. J., Schipani, E., Giaccia, A. J. 2012; 149 (1): 63-74

    Abstract

    Osteoblasts are an important component of the hematopoietic microenvironment in bone. However, the mechanisms by which osteoblasts control hematopoiesis remain unknown. We show that augmented HIF signaling in osteoprogenitors results in HSC niche expansion associated with selective expansion of the erythroid lineage. Increased red blood cell production occurred in an EPO-dependent manner with increased EPO expression in bone and suppressed EPO expression in the kidney. In contrast, inactivation of HIF in osteoprogenitors reduced EPO expression in bone. Importantly, augmented HIF activity in osteoprogenitors protected mice from stress-induced anemia. Pharmacologic or genetic inhibition of prolyl hydroxylases1/2/3 in osteoprogenitors elevated EPO expression in bone and increased hematocrit. These data reveal an unexpected role for osteoblasts in the production of EPO and modulation of erythropoiesis. Furthermore, these studies demonstrate a molecular role for osteoblastic PHD/VHL/HIF signaling that can be targeted to elevate both HSCs and erythroid progenitors in the local hematopoietic microenvironment.

    View details for DOI 10.1016/j.cell.2012.01.051

    View details for Web of Science ID 000302235400010

    View details for PubMedID 22464323

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