Diane McVey Ward, PhD
- Cell Biology
- Departments: Pathology - Research Associate Professor
- Divisions: Microbiology and Immunology
Academic Office Information
School of Medicine
30 N 1900 E
Salt Lake City, UT 84132
Research StatementOur research focuses on two major areas. First, we are interested in iron metabolism. Iron is an element required by virtually all organisms. The facile ability of iron to gain and loose electrons renders this metal an essential cofactor in redox reactions. Organisms as disparate as prokaryotes and mammals have developed a variety of mechanisms to obtain iron and regulate its storage and utilization. We utilize yeast as a model system to study iron metabolism because of the relative ease of genetic manipulation. We have utilized a variety of genetic screens to identify yeast genes required for iron transport across the plasma membrane for iron storage in the yeast vacuole. We have also identified molecules that respond to both high and low iron and regulate the transcription of iron transporters. Our studies in yeast have led to the identification of both plant and mammalian iron transporters.
We have also identified the mechanisms underlying both the regulation and malregulation of mammalian iron-linked disorders. We determined that entry of iron from cells into plasma is dependent upon the interaction of the iron exporter ferroportin with the peptide hormone hepcidin. Hepcidin is synthesized by the liver in response to inflammation and iron stores and is a negative regulator of plasma iron. We determined that hepcidin binds to ferroportin inducing its internalization and degradation. Mammalian iron overload disease is the result of either inadequate hepcidin production or mutations in ferroportin that lead to hepcidin resistance. Our current studies have identified the mechanism of hepcidin-mediated ferroportin internalization and degradation.
Our second area of research is the study of membrane trafficking. We are interested in identifying molecules that regulate the fusion and fission of endocytic vesicles. Many human diseases result from alterations vesicle trafficking and delivery to the lysosomes. One such disease is Chediak-Higashi syndrome in which lysosomes are abnormally large. We have identified the gene responsible for this disorder and have ongoing studies to identify the biochemical defect responsible for the enlargement of lysosomes.
|Postdoctoral Fellowship||University of Utah
|Doctoral Training||University of Utah
|Undergraduate||Brigham Young University
- Zhu, W, Shi, DS, Winter, JM, Rich, BE, Tong, Z, Sorensen, LK, Zhao, H, Huang, Y, Tai, Z, Mleynek, TM, Yoo, JH, Dunn, C, Ling, J, Bergquist, JA, Richards, JR, Jiang, A, Hartnett, ME, Ward, DM, Mueller, AL, Ostanin, K, Thomas, KR, Odelberg, SJ and Li, DY (2017). ARF6 is an actionable node that controls VEGFR2 trafficking and signaling in Diabetic Retinopathy. J Clin Invest.
- Alexander, M, Ramstead, A, Bauer, K, Runtsch, MC, Wallace, J, Huffaker, TB, Larsen, DK, Tolmachova, T, Seabra, MC, Round, JL, Ward, DM and OConnell, RM (2017). Rab27-dependent exosome production inhibits chronic inflammation and enables acute responses to inflammatory stimuli. J Immunol, 199(10), 3559-3570.
- Feldkamp, ML, Ward, DM, Pysher, TJ and Chambers, CT (2017). Chlamydia trachomatis is responsible for lipid vacuolation in the amniotic epithelium of fetal gastroschisis. Birth Defects Res, 109(13), 1003-1010.
- Seguin, A, Takahashi-Makise, N, Yien, YY, Huston, NC, Whitman, JC, Musso, G, Wallace, JA, Bradley, T, Bergonia, H, Kafina, MD, Matsumoto, M, Igarashi, K, Phillips, JD, Paw, BH, Kaplan, J and Ward, DM (2017). Reductions in the mitochondrial ABC transporter Abcb10 affect the transcriptional profile of heme biosynthesis genes. J Biol Chem, 292(39), 16284-16299.
- Li, L, Kaplan, J and Ward, DM (2017). The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast. J Biol Chem, 292(37), 15577-15586.
- Yaish HM, Farrell CP, Christensen RD, MacQueen BC, Jackson LK, Trochez-Encisco J, Kaplan J, Ward DM, Salah WK, Phillips JD (2017). Two novel mutations in TMPRSS6 associated with irion-refractory iron deficiency anemia in a mother and child. Blood Cells Mol Dis, 65, 38-40.
- Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Ward DM, et al (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222.
- MacQueen BC, Christense RD, Ward DM, Yaish HM, Bennett ST, OBrien EA, Sheffied MJ, Baer VL, Now GL, Weaver Lewis K, Fleming RE, and Kaplan J (2016). The iron status at birth of neonates who are "at risk" for developing iron deficiency; a pilot study. J Perinatol, 1-5.
- Alexander M, Hu R, Runtsch MC, Kaegle DA, Round JL, Ward DM, and OConnell R (2015). Exosome-delivered microRNAs reprogram the inflammatory response to endotoxin. Nat Commun, 6, 7321.
- Ben-Othman R, Flannery A Miguel, Ward DM, Kaplan J and Andrews NW (2014). Leishmania-mediated inhibition of iron export promotes parasite replication in macrophages. PLoS Pathog, 10(1), e1003901.
- Chung J, Anderson SA, Gwynn B, Deck KM, Chen MJ, Langer NB, Shaw GC, Huston NC, Boyer LA, Datta S, Paradkar PN, Li L, Wei Z, Lambert AJ, Sahr K, Wittig JG, Chen W, Lu W, Galy B, Schlaeger TM, Hentze MW, Ward DM, Kaplan J, Eisenstein RS, Peters LL, Paw BH (04/01/2014). Iron Regulatory Protein-1 protects against mitoferrin1-deficient Porphyria. J Biol Chem, 289(11), 7835-7843.
- Li L, Miao R, Jia X, Ward DM, and Kaplan J (2014). Expression of the yeast cation diffusion facilitators Mmt1 and Mmt2 affects mitochondrial and cellular iron homeostasis: evidence for mitochondrial iron export. J Biol Chem, 289(24), 17132-17141.
- White C, Yuan X, Schmidt PJ, Bresciani E, Samuel TK, Campagna D, Hall C, Bishop K, Calicchio ML, Lapierre A, Ward DM, Liu P, Fleming MD, Hamza I (2013). HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metab, 17(2), 261-70.
- Chen, C, Garcia-Santos, D, Ishikawa, Y, Sequin, A, Fegan, KH, Hildick-Smith, GJ, Cooney, JD, Chen, W, King, MJ, Schultz, IJ, Dalton, AJ, Kingsley, PD, Palis, J, Hattangadi, SM, Lodish, HF, Ward DM, Kaplan, J, Maeda, T, Ponka, P, Paw, BH (2013). Snx3 regulates recycling of the transferring receptor and iron assimilation. Cell Metab, 17, 343-352.
- Bagley DC, Paradkar PN, Durchfort N, Kaplan J, Ward DM (2012). Mon1a protein acts in trafficking through the secretory apparatus. J Biol Chem, 287, 25577-25588.
- Durchfort N, Verhoef S, Vaughn MB, Shrestha R, Adam D, Kaplan J, Ward DM (2012). The enlarged lysosomes in beige cells result from decreased lysosome fission and not increased lysosome fusion. Traffic, 13, 108-119.
- Troadec MB, Warner DE, Wallace J, Phillips J, Paw BH, Ward DM, and Kaplan J (2011). Selective loss of mitoferrin 1 in mouse tissues reveals organ specific defects. Blood, 117, 5494-5502.
- Li, L and Ward, DM (12/15/17). Iron Toxicity in Yeast: Transcriptional Regulation of the Vacuolar Iron Importer Ccc1. [Review]. Current Genetics.
- Kaplan J, Ward DM (2013). The essential nature of iron usage and regulation: variations on a theme. [Review]. Current Biology, 15, :R642-64.
- Shrestha R, Kaplan J, Ward DM (2017). Conventional and Secretory Lysosomes. In Encyclopedia of Cell Biology (2, pp. 225-234).
- Kaplan J, Ward DM (2013). Molecular Genetics of Chediak–Higashi Syndrome [Web]. Wiley Online Library- eLS (Invited Review). Available: www.els.net.