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School of Pharmacy Division of Pharmacognosy

Yu-Dong Zhou

Photo of Dr. Zhou

Research Associate Professor of Pharmacognosy

Dr. Zhou received her B.S. in Biochemistry at Fudan University (Shanghai, PR China), M.S. and Ph.D. in Biochemistry and Molecular Biology at Emory University in Atlanta, Georgia. Following postdoctoral training in the Department of Biochemistry at the University of Texas Southwestern Medical Center at Dallas, she moved to the University of Mississippi and joined the National Center for Natural Products Research (NCNPR) in 1998. She joined the Department of Pharmacognosy in 2005, and in 2007 was appointed as a Research Assistant Professor of Pharmacognosy. In July of 2010, she was appointed as a Research Associate Professor of Pharmacognosy.

email: ydzhou@olemiss.edu

Click here to see Research in Progress and Publications

  • Research in Progress

  • The focus of Dr. Zhou's research is the discovery and characterization of small molecule natural products that regulate hypoxia signaling in mammalian cells. Hypoxia (decrease in oxygen tension) occurs under a number of pathological conditions and can affect a variety of organs that range from the brain to the heart. Our current research is to discover and characterize small molecule natural product regulators of hypoxia-inducible factors (HIFs), transcription factors that regulate cellular adaptation and survival under hypoxic conditions. The three major components of our research are: 1) cell-based screening of natural product-rich extracts and pure compounds for regulators of HIF activities; 2) molecular characterization of natural product-based HIF regulators, identified through bioassay-guided isolation and structure elucidation; 3) investigation of cellular oxygen sensing and hypoxia signaling, employing natural products as molecular probes. Using this natural product chemistry-based approach, we have discovered an array of small molecule natural products that regulate HIF activities. Current projects are aimed at the molecular investigation of these natural products. This research employs a combination of biochemical, cell biological, and molecular biological methods. Funding for our research is provided by NIH/NCI, NOAA, and the DOD.

    "Samples" of Ongoing Research

    Figure 1 Figure 1. Characterization of a novel inhibitor (compound 1) of mitochondrial electron transport chain complex I. Copyright Yu-Dong Zhou 2009-2010.

     

    Figure 2

    Figure 2. Methylalpinumisoflavone (compound 2) and rotenone (compound 3) inhibit hypoxia-stimulated tumor angiogenesis in vitro.

    Figure 3

    Figure 3. Compound 1 inhibitis HIF-1 activation by blocking the induction of nuclear HIF-1a protein. Copyright Yu-Dong Zhou 2009-2010.

  • Representative Publications

    Nagle, D.G.; Zhou, Y.-D."Natural Products as Probes of Selected Targets in Tumor Cell Biology and Hypoxic Signaling" Chapter 2.23 in Comprehensive Natural Products Chemistry II, Mander, L.N. ed. in chief; Vol. 2: Structural Diversity II – Secondary Metabolite Sources, Evolution, and Selected Molecular Structures, Moore, B.S., Crews, P., Vol. eds., Elsevier, Oxford, 2009, In Press

    Nagle, D.G.; Zhou, Y.-D.  “Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors”  Phytochemistry Reviews, 2009, In Press.

    Liu, Y.; Veena, C.K.; Morgan, J.B.; Mohammed, K.A.; Jekabsons, M.B.; Nagle, D.G.; Zhou, Y.-D.Methylalpinumisoflavone Inhibits Hypoxia-inducible Factor-1 (HIF-1) Activation by Simultaneously Targeting Multiple Pathways .”  Journal of Biological Chemistry, 2009, 284, 5859-5868.

    Liu, Y.; Liu, R.; Mao, S.-C.; Morgan, J.B.; Jekabsons, M.B.; Zhou, Y.-D.; Nagle, D.G.  “Molecular-Targeted Antitumor Agents 19: Furospongolide from a Marine Lendenfeldia sp. Sponge Inhibits Hypoxia-Inducible Factor-1 (HIF-1) Activation in Breast Tumor Cells.”  Journal of Natural Products, 2008, 71, 1854-60.

    El Sayed, K.A.; Shallal, H.M.; Khanfar, M.; Muralidharan, A; Awate, B.; Youssef, D.T.A.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G.; Shah, G.  “Latrunculin A and its 17-O-carbamates inhibit prostate tumor cell invasion and HIF-1 activation in breast tumor cells.”  Journal of Natural Products, 2008, 71, 1854-1860.

    Chittiboyina, A.G.; Gundluru, M.K.; Carvalho, P.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G.; Avery, M.A.  “Total Synthesis and Absolute Configuration of Laurenditerpenol: A HIF-1 Activation Inhibitor.”  Journal of Medicinal Chemistry, 2007, 50, 6299-6302.

    Dai, J.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G.  “Cytotoxic metabolites from an Indonesian sponge Lendenfeldia sp.”  Journal of Natural Products,2007, 70, 1824–1826.

    Liu, R.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G.  “Molecular-targeted antitumor agents 15: Neolamellarins from the marine sponge Dendrilla nigra inhibit hypoxia-inducible factor-1 (HIF-1) activation and secreted vascular endothelial growth factor (VEGF) production in breast tumor cells.”  Journal of Natural Products,2007, 70, 1741–1745.

    Dai, J.; Liu, Y.; Jia, H.; Zhou, Y.-D.; Nagle, D.G.  “Benzochromenones from the marine crinoid Comantheria rotula inhibit hypoxia-inducible factor-1 (HIF-1) reporter activity and differentially suppress the growth of certain tumor cell lines.”  Journal of Natural Products,2007, 70, 1462-1466.

    Dai, J.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G.  “Hypoxia-selective antitumor Agents:  Norsesterterpene peroxides from the marine sponge Diacarnus levii preferentially suppress the growth of tumor cells under hypoxic conditions.”  Journal of Natural Products, 2007, 70, 130-133.

    Dai, J.; Fishback, J.A.; Zhou, Y.-D.; Nagle, D.G.  “Sodwanone and yardenone triterpenes from a South African species of the marine sponge Axinella inhibit hypoxia-inducible factor-1 (HIF-1) Activation in both Breast and Prostate Tumor Cells.”  Journal of Natural Products,2006, 69, 1715-1720.

    Nagle, D.G; Ferreira, D.; Zhou, Y.-D.  “Molecules of interest: Epigallocatechin-3-Gallate (EGCG): Chemical and biomedical perspectives.”  Phytochemistry, 2006, 67, 1849-1855.

    Nagle, D.G.; Zhou, Y.-D.  “Natural product-derived small molecule activators of hypoxia-inducible factor-1 (HIF-1).”  Current Pharmaceutical Design, 2006, 12, 2673-2688.

    Nagle, D.G.; Zhou, Y.-D.  “Natural product-based inhibitors of hypoxia-inducible factor-1 (HIF-1).”  Current Cancer Drug Targets, 2006, 7, 355-369.

    Mora, F.D; Jones, D.K.; Desai, P.V.; Patny, A.; Avery, M.A.; Feller, D.R.; Smillie, T.; Zhou, Y.-D.; Nagle, D.G.  “Bioassay for the identification of natural product-based activators of peroxisome proliferator-activated receptor-g (PPARg): Themarine sponge metabolite psammaplin A activates PPARg and induces apoptosis in human breast tumor cells.”  Journal of Natural Products, 2006, 69, 547-552. 

    Hossain, C.F.; Kim, Y.-P.; Baerson, S.R.; Zhang, L.; Bruick, R.K.; Mohammed, K.A.; Agarwal, A.K.; Nagle, D.G.; Zhou, Y.-D. Saururus cernuus lignans - Potent small molecule inhibitors of hypoxia-inducible factor-1.”  Biochemical and Biophysical Research Communications, 2005, 333, 1026-1033.

    Zhou, Y.-D.; Kim, Y.-P.; Mohammed, K.A.; Jones, D.K.; Muhammad, I.: Dunbar, D.C.; Nagle, D.G.  “The terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-Inducible factor-1 (HIF-1) in breast tumor cells.”  Journal of Natural Products,2005, 68, 947-950.

    Zhou, Y.-D.; Kim, Y.-P.; Li, X.-C.; Baerson, S.R.; Agarwal, A.K.; Hodges, T.W.; Ferreira, D.; Nagle, D.G.  “Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: Potential adverse effects of cancer chemoprevention with high-dose green tea extracts.”  Journal of Natural Products, 2004, 67, 2063-2069.

    Mohammed, K.A.; Hossain, C.F.; Zhang, L.; Bruick, R.K.; Zhou, Y.-D.; Nagle, D.G.  “Laurenditerpenol, a new diterpene from the tropical marine alga Laurencia intricata potently inhibits HIF-1 mediated hypoxic signaling in breast tumor cells.”  Journal of Natural Products, 2004, 67, 2002-2007.  (Jack L. Beal Award winning manuscript - American Society of Pharmacognosy)

    Erbel-Sieler, C.; Dudley, C.; Zhou, Y.; Wu., X.; Estill, S.J.; Han, T.; Diaz-Arrastia, R.; Brunskill, E.W.; Potter, S.S.; McKnight, S.L.  “Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.”  Proceedings of the National Academy of Sciences USA, 2004, 101, 13648-13653.  (┴Equal contribution of authors)

    Hodges, T.W.; Hossain, C.F.; Kim, Y.-P.; Zhou, Y.-D.; Nagle, D.G.  “Molecular-targeted antitumor agents: the Saururus cernuus dineolignans manassantin B and 4-O-demethylmanassantin B are potent inhibitors of hypoxia-activated HIF-1.”  Journal of Natural Products, 2004, 67, 767-771.

    Nagle, D.G.; Zhou, Y.-D.; Mora, F.D.; Mohammed, K.A.; Kim, Y.-P.  “Mechanism targeted discovery of antitumor marine natural products.”  Current Medicinal Chemistry, 2004, 11, 1725-1756.