Yrd. Doç. Dr. Ibrahim YAMAN
Moleküler Biyoloji ve Genetik
Kuzey Park, 318
34342 Bebek - Istanbul
+90 (212) 359 7557
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Molecular mechanisms underlying carcinogenicity of mycotoxins
Mycotoxins are secondary metabolites that are produced by filamentous fungi, which mainly belong to Aspergillus, Penicillium and Fusarium genera. Deterioration of liver or kidney functions and in extreme cases death are among the acute effects of mycotoxins. The most important chronic effect of many mycotoxins is the induction of cancer development, especially in the liver and kidney tissues. The studies conducted in my lab are focused on identification of molecular mechanisms leading to induction of cancer by mycotoxin Ochratoxin A (OTA) using an integrative toxicogenomic approach including transcriptomics and proteomics. These studies will further advance our understanding of the mechanism(s) of OTA carcinogenicity and signal transduction pathways.
Regulation of Gene Expression under Chemotoxic Stress
he second line of work in our lab involves analyzes of the regulation of gene expression under stress conditions. Eukaryotic cells have developed multiple mechanisms to respond to different cellular stresses initiated by chemical toxins. The regulations of gene expression at transcriptional and post-transcriptional levels are very important modules of the cellular stress response. Our preliminary studies and the work that was done by others have shown that OTA treatment causes increased expression of Kim1 (Kidney Injury Molecule 1 which is also known as HavcR1) mRNA and protein in kidney cell lines and animal models such as mouse . Therefore our aim is to understand how cells achieve high-level of Kim1 expression while there is a decrease in the expression of other genes at the global level.
- Özcan Z, Gül G, Yaman I (2015) Ochratoxin A activates opposing c-MET/PI3K/Akt and MAPK/ERK 1-2 pathways in human proximal tubule HK-2 cells.
Arch Toxic. 89(8):1313-27. doi: 10.1007/s00204-014-1311-x.
- Majumder M, Yaman I , Gaccioli F, Zeenko VV, Wang C, Caprara MG, Venema RC, Komar AA, Snider MD, Hatzoglou M. (2009) The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation.
Mol Cell Biol. 2009, 29(10):2899-912.
- Alex B. Lopez, Chuanping Wang, Charlie C. Huang, Ibrahim Yaman , Yi Li, Kaushik Chakravarty, Peter F. Johnson, Cheng-Ming Chiang, Martin D. Snider, Ronald C. Wek and Maria Hatzoglou (2006) A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation.
- Fernandez J, Yaman I, Huang C, Liu H, Lopez A B, Komar A A, Caprara M G, Merrick W G, Snider M D, Kaufman R J, Lamers W H, and Hatzoglou M (2005)
Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation.
Mol. Cell. 17(3):405-16.
- Hatzoglou M, Fernandez J, Yaman I, Closs E. (2004) Regulation of cationic amino acid transport: the story of the CAT-1 transporter.
Annu Rev Nutr 24:377-99.
- Fernandez J, Lopez AB, Wang C, Mishra R, Zhou L, Yaman I, Snider MD, Hatzoglou M (2003) Transcriptional control of the arginine/lysine transporter, cat-1, by physiological stress.
J Biol Chem. 278(50):50000-9.
- Yaman I*, Fernandez J*, Liu H, Caprara M, Komar AA, Koromilas AE, Zhou L, Snider MD, Scheuner D, Kaufman RJ, Hatzoglou M. (2003) The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leader. (*Equal contribution)
Cell 2003, 113(4):519-31.
- Yaman I, Fernandez J, Sarkar B, Schneider RJ, Snider MD, Nagy LE, Hatzoglou M (2002) Nutritional control of mRNA stability is mediated by a conserved AU-rich element that binds the cytoplasmic shuttling protein HuR.
J Biol Chem. 277(44):41539-46.
- Fernandez J, Yaman I, Sarnow P, Snider MD, Hatzoglou M. (2002) Regulation of internal ribosomal entry site-mediated translation by phosphorylation of the translation initiation factor eIF2alpha.
J Biol Chem. 2002, 277(21):19198-205.
- Fernandez J, Yaman I, Merrick WC, Koromilas A, Wek RC, Sood R, Hensold J, Hatzoglou M (2002) Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame.
J Biol Chem. 277(3):2050-8.
- Fernandez J, Yaman I, Mishra R, Merrick WC, Snider MD, Lamers WH, Hatzoglou M (2001) Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability.
J Biol Chem. 276(15):12285-91.