Tolunay Beker Aydemir, Ph.D. is an Assistant Professor of Molecular Nutrition at Cornell University Division of Nutritional Sciences. She graduated from Ankara University with a BS degree in Biology. She obtained her Ph.D. degree in Biomedical Sciences with a concentration in Biochemistry and Molecular Biology at the University of Florida College of Medicine. She completed her postdoctoral studies in the Nutritional Genomics Laboratory, Center for Nutritional Sciences at University of Florida.
Aydemir research group is aimed at developing a greater understanding of how zinc and manganese function to regulate different cellular processes central to maintaining homeostasis, and thus health. Our recent research specifically focuses on understanding the mechanistic link between the function of the metal transporter ZIP14 and the development of manganese-induced neurodegeneration and parkinsonism.
Our overall research interests center on how transporter-mediated zinc and manganese mobilization function to regulate diverse cellular processes in health and disease.
1- Zinc is an essential micronutrient which is now recognized as a signaling molecule in addition to its well-characterized regulatory, catalytic, and structural roles. The maintenance of zinc homeostasis and the targeted cellular function of zinc is facilitated by two families of metal transporters, ZIP and ZnT. ZIP14/SLC39A14 is a ZIP family member, which traffics metals into the cytoplasm. Whole-body knockout (KO) of the Zip14 in mice alters zinc homeostasis and creates a phenotype with key features of metabolic endotoxemia (low-grade chronic inflammation). This signature includes increased intestinal permeability, elevated serum endotoxin levels, increased adiposity coupled with up-regulated cytokine expression and insulin insensitivity in adipose tissue, and enlarged pancreatic islets with greater serum insulin. Using both in vitro cell culture systems and in vivo whole-body and tissue-specific conditional (intestine, pancreatic beta-cells, and liver) Zip14 KO mouse models we aim to answer three main questions:
- What is the role of ZIP14-mediated zinc transport in intestinal barrier function, specifically in the gut microbiota profile and corresponding host response?
- What is the role of ZIP14-mediated zinc transport in pancreatic insulin biosynthesis and secretion?
- What is the role of ZIP14-mediated zinc transport in hepatic glucose metabolism?
2- Manganese (Mn) is an essential micronutrient. Impaired Mn homeostasis results in excess Mn and neurotoxicity. ZIP14/SLC39A14 is a ZIP family transmembrane protein that regulates intracellular manganese and iron in addition to Zn. Recently, it has been shown that humans carrying ZIP14 mutations develop childhood-onset parkinsonism and dystonia. This phenotype was recapitulated in Zip14 knockout (KO) mice. However, the mechanism of ZIP14-mediated Mn detoxification and how defective ZIP14 function leads to Mn overload, systemic and neuroinflammation have not been well-characterized. Using whole-body and intestine-specific Zip14 KO mouse models, we will investigate the organ/tissue-specific role of ZIP14-mediated Mn transport in Mn homeostasis. The three main aims are:
- Determine if ZIP14 at the BL membrane of enterocytes provides an alternate route for systemic Mn detoxification.
- Determine if ZIP14 at the BL membrane of brain endothelial cells regulates Mn detoxification and if defective ZIP14 function leads to neuroinflammation and neurodegeneration.
- Determine if impaired intestinal barrier function and low-grade chronic inflammation in Zip14 KO mice contribute to ZIP14-associated parkinsonism.
Aydemir, T. B., & Cousins, R. J. (2018). The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14). The Journal of Nutrition, 148(2), 174–184. https://doi.org/10.1093/jn/nxx041
Hendrickx, G., Borra, V. M., Steenackers, E., Yorgan, T. A., Hermans, C., Boudin, E., … Van Hul, W. (2018). Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis. PLOS Genetics, 14(4), e1007321. https://doi.org/10.1371/journal.pgen.1007321
Aydemir, T. B., Kim, M.-H., Kim, J., Colon-Perez, L. M., Banan, G., Mareci, T. H., … Cousins, R. J. (2017). Metal Transporter Zip14 ( Slc39a14 ) Deletion in Mice Increases Manganese Deposition and Produces Neurotoxic Signatures and Diminished Motor Activity. The Journal of Neuroscience, 37(25), 5996–6006. https://doi.org/10.1523/JNEUROSCI.0285-17.2017
Kim, M.-H., Aydemir, T. B., Kim, J., & Cousins, R. J. (2017). Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress. Proceedings of the National Academy of Sciences, 201704012. https://doi.org/10.1073/pnas.1704012114
Aydemir, T. B., Troche, C., Kim, J., Kim, M.-H., Teran, O. Y., Leeuwenburgh, C., & Cousins, R. J. (2016). Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion. Experimental Gerontology, 85, 88–94. https://doi.org/10.1016/j.exger.2016.09.013
Kim, M.-H., Aydemir, T. B., & Cousins, R. J. (2016). Dietary Zinc Regulates Apoptosis through the Phosphorylated Eukaryotic Initiation Factor 2 /Activating Transcription Factor-4/C/EBP-Homologous Protein Pathway during Pharmacologically Induced Endoplasmic Reticulum Stress in Livers of Mice. Journal of Nutrition, 146(11), 2180–2186. https://doi.org/10.3945/jn.116.237495
Aydemir, T. B., Troche, C., Kim, M.-H., & Cousins, R. J. (2016). Hepatic ZIP14-mediated Zinc Transport Contributes to Endosomal Insulin Receptor Trafficking and Glucose Metabolism. Journal of Biological Chemistry, 291(46), 23939–23951. https://doi.org/10.1074/jbc.M116.748632
Troche, C., Aydemir, T. B., & Cousins, R. J. (2016). Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity. American Journal of Physiology. Endocrinology and Metabolism, 310(4), E258-68. https://doi.org/10.1152/ajpendo.00421.2015
Lais, L. L., de Lima Vale, S. H., Xavier, C. A., de Araujo Silva, A., Aydemir, T. B., & Cousins, R. J. (2016). Effect of A One-Week Balanced Diet on Expression of Genes Related to Zinc Metabolism and Inflammation in Type 2 Diabetic Patients. Clinical Nutrition Research, 5(1), 26–32. https://doi.org/10.7762/cnr.2016.5.1.26
Guthrie, G. J., Aydemir, T. B., Troche, C., Martin, A. B., Chang, S.-M., & Cousins, R. J. (2015). Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function. American Journal of Physiology. Gastrointestinal and Liver Physiology, 308(3), G171-8. https://doi.org/10.1152/ajpgi.00021.2014
Martin, A. B., Aydemir, T. B., Guthrie, G. J., Samuelson, D. A., Chang, S.-M., & Cousins, R. J. (2013). Gastric and colonic zinc transporter ZIP11 (Slc39a11) in mice responds to dietary zinc and exhibits nuclear localization. The Journal of Nutrition, 143(12), 1882–1888. https://doi.org/10.3945/jn.113.184457
Aydemir, T. B., Sitren, H. S., & Cousins, R. J. (2012). The zinc transporter Zip14 influences c-Met phosphorylation and hepatocyte proliferation during liver regeneration in mice. Gastroenterology, 142(7), 1536–46.e5. https://doi.org/10.1053/j.gastro.2012.02.046
Ryu, M.-S., Guthrie, G. J., Maki, A. B., Aydemir, T. B., & Cousins, R. J. (2012). Proteomic analysis shows the upregulation of erythrocyte dematin in zinc-restricted human subjects. The American Journal of Clinical Nutrition, 95(5), 1096–1102. https://doi.org/10.3945/ajcn.111.032862
Aydemir, T. B., Chang, S.-M., Guthrie, G. J., Maki, A. B., Ryu, M.-S., Karabiyik, A., & Cousins, R. J. (2012). Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia). PloS One, 7(10), e48679. https://doi.org/10.1371/journal.pone.0048679
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009). Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-gamma expression in activated human T cells. Journal of Leukocyte Biology, 86(2), 337–348. https://doi.org/10.1189/jlb.1208759
Aydemir, T. B., Blanchard, R. K., & Cousins, R. J. (2006). Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations. Proceedings of the National Academy of Sciences of the United States of America, 103(6), 1699–1704. https://doi.org/10.1073/pnas.0510407103
Liuzzi, J. P., Lichten, L. A., Rivera, S., Blanchard, R. K., Aydemir, T. B., Knutson, M. D., … Cousins, R. J. (2005). Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proceedings of the National Academy of Sciences of the United States of America, 102(19), 6843–6848. https://doi.org/10.1073/pnas.0502257102
I believe that being able to transmit knowledge and share my passion with students is a privilege in life. I know that my passion for learning will never end, and I hope I can transmit this to my current and future students.
Ankara University Science Faculty B.S. Biology
Ankara University School of Medicine M.S. Molecular Hepatology
University of Florida, College of Medicine Ph.D. Biochemistry and Molecular Biology
University of Florida, Center for Nut. Sci. Postdoc. Nutritional Genomics Laboratory