Ningning Zhao, PhD

Associate Professor, School of Nutritional Sciences and Wellness

EDUCATION & PROFESSIONAL TRAINING:

  • Postdoctoral Researcher, Cell Biology, Oregon Health & Science University
  • Ph.D., Nutritional Sciences (Molecular Nutrition), University of Florida
  • M.Ed., Sports Science (Sports Nutrition and Exercise Biochemistry), Beijing Sport University
  • B.S., Sports Science (Exercise Biochemistry), Beijing Sport University

RESEARCH & INTERESTS:

Summary of Current Research

The work in our Lab is focused on advancing molecular mechanisms for the function and regulation of plasma membrane metal transporters. These transporters play fundamental roles in regulating cellular metabolism and cellular function. Mutations and malfunctioning of these transporters are directly pertinent to the initiation and the progression of an increasing number of human diseases, including iron deficiency, hemochromatosis, cancer, and childhood on-set neurodegeneration. We identify and characterize the genes and factors that are involved in determining the structure and function of these metal transporters. We also examine the intracellular trafficking and degradation of these proteins.

In our research, we combine cell-line and mouse models, and employ a variety of biochemical and molecular biology techniques. We also utilize the cutting-edge genome engineering technologies, including Adeno-Associated Virus-mediated genomic modification and CRISPR/Cas9-mediated genome editing. We hope that our research will advance the understanding of disease mechanisms, identify therapeutic target genes, and improve the life quality of patients.

Join Our Lab

Welcome! We are seeking energetic and highly motivated researchers, including graduate students and postdoctoral researchers. If interested, please send an inquiry about openings to zhaonn@email.arizona.edu and attach your CV and personal statement (please highlight your academic background and research experience in the statement).

Students should apply to a graduate program at the UA. Graduate students already enrolled at the UA and are interested in rotating in the lab can contact Ningning directly. A list of three references is required for postdoctoral applicants.

Selected Publications (*corresponding author)

  • Lewis SA, Shetty S, Gamble S, Heim J, Zhao N, Stitt G, Pankratz M, Mangum T, Marku I, Rosenberg RB, Wilfong AA, Fahey MC, Kim S, Myers SJ, Appavu B, Kruer MC. Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation. Orphanet Journal of Rare Diseases2023; 18(1): 225. PMID: 37537625. PMCID: PMC10398931.
  • Liu Q, Jenkitkasemwong S, Prami TA, McCabe SM, Zhao N, Hojyo S, Fukada T, Knutson MD. Metal-ion transporter SLC39A8 is required for brain manganese uptake and accumulation. The Journal of Biological Chemistry2023; 299(8): 105078. PMID: 37482277. PMCID: PMC10457451.
  • Vungutur V, Yu S, McCabe S, Fung C, Zhao N*. A simple and highly reproducible method for the detection of erythrocyte membrane ZIP metal transporters by immunoblotting. Methods in Enzymology2023; 687: 87-102. PMID: 37666640. PMCID: PMC10755855.
  • McCabe S, Limesand K, Zhao N*. Recent progress toward understanding the role of ZIP14 in regulating systemic manganese homeostasis. Computational and Structural Biotechnology Journal2023; 21: 2332-2338. PMID: 37020930. PMCID: PMC10070054.
  • Yu S, Zhao N*. The Regulation of ZIP8 by Dietary Manganese in Mice.  International Journal of Molecular Sciences 2023; 24(6). PMID: 36983036. PMCID: PMC10056016.
  • Fung CK, Zhao N*. The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice. International Journal of Molecular Sciences 2022; 23(12).  PMID: 35742937. PMCID: PMC9223378
  • Wu Y, Wei G, Zhao N*, Restriction of manganese intake prevents the onset of brain manganese overload in Zip14–/– mice, International Journal of Molecular Sciences2021; 22(13): 6773. PMID: 34202493. PMCID: PMC8268934.
  • McCabe SM, Zhao N*, The potential roles of blood-brain barrier and blood-cerebrospinal fluid barrier in maintaining brain manganese homeostasis, Nutrients2021; 13(6). PMID: 34072120. PMCID: PMC8227615.
  • Wei G, Wu Y, Zhao N*, Generation of a polyclonal antibody against the mouse metal transporter ZIP8, Antibodies2021; 10(2):16. PMID: 33919173. PMCID: PMC8167614.
  • Morgan SE, Schroten H, Ishikawa H, Zhao N*, Localization of ZIP14 and ZIP8 in HIBCPP cells. Brain Sciences2020; 10(8): 534. PMID: 32784388. PMCID: PMC7464652.
  • Winslow JWW, Limesand KH, Zhao N*, The functions of ZIP8, ZIP14, and ZnT10 in the regulation of systemic manganese homeostasis. International Journal of Molecular Sciences2020; 21(9): 3304. PMID: 32392784. PMCID: PMC7246657.
  • Felber DF, Wu Y, Zhao N*, Regulation of metal transporter, ZIP14 and ZnT10, by manganese intake in mice. Nutrients2019; 11(9): 2099. PMID: 31487869. PMCID: PMC6770778.
  • Scheiber IF, Alarcon NO, Zhao N*, Manganese uptake by A549 cells is mediated by both ZIP8 and ZIP14. Nutrients2019; 11(7): 1473. PMID: 31261654. PMCID: PMC6682971.
  • Scheiber IF, Wu Y, Morgan SE, Zhao N*, The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. The Journal of Biological Chemistry2019; 294(23): 9147-9160. PMID: 31028174. PMCID: PMC6556583.
  • Zhao N*, Zhang AS, Wortham AM, Jue S, Knutson MD, and Enns CA, The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14. Nutrients2017; 9(12): 1335. PMID: 29292794. PMCID: PMC5748785.
  • Wahedi M, Wortham AM, Kleven MD, Zhao N, Jue S, Enns CA, Zhang AS. Matriptase-2 Suppresses Hepcidin Expression by Cleaving Multiple Components of the Hepcidin Induction Pathway. The Journal of Biological Chemistry, 2017; 292(44):18354-18371. PMID: 28924039. PMCID: PMC5672056.
  • Zhao N, Maxson JE, Zhang RH, Wahedi M, Enns CA, and Zhang AS. Neogenin Facilitates the Induction of Hepcidin Expression by Hemojuvelin in the Liver. The Journal of Biological Chemistry2016; 291(23): 12322-12335. PMID: 27072365. PMCID: PMC4933279.
  • Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, et al. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia. Nature Communications2016; 7:11601. PMID: 27231142. PMCID: PMC4894980.
  • Zhao N, Nizzi CP, Anderson SA, Wang J, Ueno A, Tsukamoto H, Eisenstein RS, Enns CA and Zhang AS. Low intracellular iron increases the stability of matriptase-2. The Journal of Biological Chemistry2015; 290(7): 4432-4446. PMID: 25550162. PMCID: PMC4326848.
  • Zhao N, Zhang AS, Worthen C, Knutson MD, and Enns CA. An iron-regulated and glycosylation- dependent proteasomal degradation pathway for the plasma membrane metal transporter ZIP14. Proceedings of the National Academy of Sciences of the United States of America2014; 11(25): 9175-9180. PMID: 24927598. PMCID: PMC4078863.
  • Zhao N, Zhang AS and Enns CA. Iron regulation by hepcidin. Journal of Clinical Investigation2013; 123 (6): 2337-2343. PMID: 23722909. PMCID: PMC3668831.
  • Zhao N and Enns CA. N-linked glycosylation is required for transferrin-induced stabilization of transferrin receptor 2, but not for transferrin binding or trafficking to the cell surface. Biochemistry2013; 52: 3310-3319. PMID: 23556518. PMCID: PMC3656769.
  • Zhao N and Enns CA. Iron transport machinery of human cells: players and their interactions. Current Topics in Membranes2012; 69: 67-93. PMID: 23046647. PMCID: PMC3934873.
  • Pinilla-Tenas JJ, Sparkman BK, Shawki A, Illing AC, Mitchell CJ, Zhao N, Liuzzi JP, Cousins RJ, Knutson MD, Mackenzie B. ZIP14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. American Journal of Physiology-Cell Physiology2011; 301(4): C862-71. PMID: 21653899. PMCID: PMC3191563.
  • Zhao N, Gao J, Enns CA, Knutson MD. ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. The Journal of Biological Chemistry2010; 285(42): 32141-32150. PMID: 20682781. PMCID: PMC2952215. 
  • Gao J, Zhao N, Knutson MD, Enns CA. The hereditary hemochromatosis protein, HFE, inhibits iron uptake via down-regulation of ZIP14 in HepG2 cells. The Journal of Biological Chemistry2008; 283(31): 21462- 21468. PMID: 18524764. PMCID: PMC2490774.