225 Savage Hall
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 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.
Peer-Reviewed Research Articles
- Lin, M., Colon-Perez, L., Sambo, D., Miller, D., Lebowitz, J., Jimenez-Rondan, F., Cousins, RJ., Horenstein, N., Aydemir, TB., Febo, M. and Khoshbouei, H. (2020). Mechanism of manganese dysregulation of dopamine neuronal activity. J Neurosci. Under Review
- Aydemir, TB*., Thorn, TL., Ruggiero, C., Pompilus, M., Febo, M. and Cousins RJ. (2020). Intestine-specific deletion of metal transporter Zip14 (Slc39a14) causes brain manganese overload and locomotor defects of manganism. Am J Physiol Gastrointest Liver Physiol. doi: 10.1152/ajpgi.00301.2019. [Epub ahead of print] PMID: 32003605. * Corresponding author
- Kim, J., Aydemir, TB., Jimenez-Rondan, F., Ruggiero, C., Kim, MH. and Cousins RJ. (2020). Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7. Scientific Reports. Under Review
- Hendrickx, G., Borra, V. M., Steenackers, E., Yorgan, T. A., Hermans, C., Boudin, E., Waterval, JJ., Jansen, IDC., Aydemir, TB., … 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.
- Kim MH, Aydemir TB, Kim J, Cousins RJ. 2017. Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress. Proc Natl Acad Sci U S A, 114:E5805–14. PMC5530682
- Aydemir TB, Kim MH, Kim J, Colon-Perez LM, Banan G, Mareci TH, Febo M Cousins RJ. 2017. Metal transporter ZIP14 (SLC39A14) deletion in mice increases manganese deposition and produces neurotoxic signatures and diminished motor activity. J Neurosci, 37:5996–6006. PMC5481939
- Aydemir TB, Troche C, Kim MH, Cousins RJ. 2016. Hepatic ZIP14-mediated zinc transport contributes to endosomal insulin receptor trafficking and glucose metabolism. J Biol Chem, 291:23939–51. PMCID: PMC5104920
- Aydemir TB, Troche C, Kim J, Kim MH, Teran OY, Leeuwenburgh C, Cousins RJ. 2016. Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion. Exp Gerontol, 85:88–94. PMCID: PMC5101137
- Kim MH, Aydemir TB, Cousins RJ. 2016. Dietary zinc regulates apoptosis through the p-elF2α/ATF4/CHOP pathway during pharmacologically induced endoplasmic reticulum stress in livers of mice. J Nutr, 146:2180–6. PMCID: PMC5086795
- Troche C, Aydemir TB, Cousins RJ. 2016. Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity. Am J Physiol Endocrinol Metab, 310(4): E258–68. PMCID: PMC4971811
- Guthrie GJ, Aydemir TB, Troche C, Martin AB, Chang SM, Cousins RJ. 2015. Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function. Am J Physiol Gastrointest Liver Physiol, 308(3): G171–8. PMCID: PMC4312952
- Martin AB, Aydemir TB, Guthrie GJ, Samuelson DA, Chang SM, Cousins RJ. 2013. Gastric and colonic zinc transporter ZIP11 (Slc39a11) in mice responds to dietary zinc and exhibits nuclear localization. J Nutr, 143(12):1882-8. PMCID: PMC3827636
- Aydemir TB, Chang SM, Guthrie GJ, Maki AB, Ryu MS, Cousins RJ. 2012 Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia). PLoS One, 7(10): e48679. doi:10.1371/journal.pone. PMCID: PMC3480510
- Aydemir TB, Sitren HS, Cousins RJ. 2012. The zinc transporter Zip14 influences c-Met phosphorylation and hepatocyte proliferation during liver regeneration in mice. Gastroenterology, 142:1536–46. PMCID: PMC3635537
- Ryu MS, Guthrie GJ, Maki AB, Aydemir TB, Cousins RJ. 2012. Proteomic analysis shows the up-regulation of erythrocyte dematin in zinc-restricted human subjects. Am J Clin Nutr, 95:1096–102. PMCID: PMC3325834
- Aydemir TB, Liuzzi JP, McClellan S, Cousins RJ. 2009. Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-gamma expression in activated human T cells. J Leukoc Biol, 86:337–48. PMCID: PMC2726764
- Aydemir TB, Blanchard RK, Cousins RJ. 2006. Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations. Proc Natl Acad Sci U S A, 103:1699–704. PMCID: PMC1413653
- Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ. 2005. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A, 102:6843–8. PMCID: PMC1100791
- Pai SB, Bozdayi AM, Pai RB, Beker T,* Sarioglu M, Turkyilmaz AR, Grier J, Yurdaydin C, Schinazi RF. 2005. Emergence of a novel mutation in the FLLA region of hepatitis B virus during lamivudine therapy. Antimicrob Agents Chemother, 49:2618–24. PMCID: PMC1168680
- Pai SB, Pai RB, Xie MY, Beker T,* Shi J, Tharnish PM, Chu CK, Schinazi RF. 2005. Characterization of hepatitis B virus inhibition by novel 2'-fluoro-2', 3'-unsaturated beta-D- and L-nucleosides. Antivir Chem Chemother, 16:183–92.
*Name changed from Beker T. to Aydemir T. due to change in marital status.
- Aydemir TB*, Cousins RJ. 2017. The multiple faces of the metal transporter ZIP14 (SLC39A14). The Journal of Nutrition, 148(2), 174–184.
* Corresponding author
- Cousins RJ, Aydemir TB, Lichten LA. 2010. Plenary Lecture 2: Transcription factors, regulatory elements and nutrient-gene communication. Proc Nutr Soc, 69:91–4. PMCID: PMC3790273
- Ryu MS, Aydemir TB. 2019. Chapter 23. Zinc. Present Knowledge in Nutrition: Basic Nutrition and Metabolism, Eleventh Edition. Elsevier
2010– Member, American Society for Nutrition
2010– Member, American Society for Biochemistry and Molecular Biology
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.
NS3450: Introduction to Physiochemical and Biological Aspects of Food
NS4010: Empirical Research (Independent Study)
NS4030: Teaching Apprenticeship (Independent Study)
B.S., Biology, Ankara University Science Faculty
M.S., Molecular Hepatology, Ankara University School of Medicine
Ph.D., Biochemistry and Molecular Biology, University of Florida, College of Medicine
Postdoc., Nutritional Genomics Laboratory, University of Florida, Center for Nut. Sci.
Graduate student admission committee