Sabire Ozcan, Ph.D.

Bio / Education: 

B.S. /M.S Heinrich-Heine University, Duesseldorf, Germany
Ph.D. Heinrich-Heine University, Duesseldorf, Germany
Postdoc. Washington University, St. Louis, Missouri

Research Description: 

Production and secretion of insulin from the beta cells of the pancreas is stimulated by increases in blood glucose levels, after each meal and this process is essential for maintaining normal glucose homeostasis.  Defects in glucose-regulated production and secretion of insulin lead to diabetes mellitus, which affects over 8% of the American population.  Our laboratory is interested in understanding the molecular mechanisms by which changes in glucose levels regulate insulin production and pancreatic beta-cell function.  The major projects in the laboratory are:

1. Glucose-regulation of insulin gene transcription in pancreatic beta cells.
Glucose-induction of insulin gene expression is regulated by a cooperative interaction of three beta-cell specific transcription factors, Pdx-1, MafA and NeuroD1.  The long-term goal of this project is to understand how glucose modulates the function of Pdx-1, MafA and NeuroD1 to stimulate insulin gene expression.

2. Role of O-linked GlcNAc protein modification in the development of diabetes.
Elevated levels of O-linked GlcNAc protein modification in response to hyperglycemia has been proposed to contribute to the secondary complications associated with diabetes, including cardiovascular disease, kidney failure, blindness etc.  However, the exact mechanisms by which increases in O-GlcNAc levels interfere with glucose homeostasis remain to be established.  This project addresses the role of O-linked GlcNAc modification of proteins in regulation of beta-cell function in the pancreas.

3. Studies on microRNA function in pancreatic beta cells.
MicroRNAs (miRNAs) are small non-coding ribonucleotides, that bind mRNAs and function as translational inhibitors.  MiRNAs have been shown to be involved in many diseases including cancer, neurodegeneration and diabetes.  We have identified several glucose-regulated miRNAs from pancreatic beta cells and are currently studying their function in insulin production and secretion.   

In summary, the information obtained in pursuit of these projects should significantly advance our understanding of how glucose regulates insulin production and insulin secretion in pancreatic beta cells, and should enable the development of new strategies for the treatment and prevention of diabetes.

Selected Publications: 

Mosley, A. L., and S. Özcan. 2003. Glucose regulates insulin gene transcription by hyperacetylation of histone H4. J. Biol. Chem. 278:19660-19666. PMID: 12665509.

Mosley, A. L., Corbett, J. A., and S. Özcan. 2004. Glucose regulation of insulin gene expression requires the recruitment of p300 by the beta-cell specific transcription factor Pdx-1. Mol. Endocrinol.18:2279-2290. PMID: 15166251.

Mosley, A. L., and S. Özcan. 2004. The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose. J. Biol. Chem. 279:54241-54247. PMID: 15496408.

März, P., J. Stetefeld, K. Bendfeldt, C. Nitsch, J. Reinstein, R. L. Shoeman, B. Dimitriades-Schmutz, M. Schwager, D. Leiser, S. Özcan, U. Otten and S. Özbek. 2006. Ataxin-10 interacts with O-linked β-N-acetylglucosamine transferase in the brain. J. Biol. Chem. 281:20263-20270. PMID: 16714295.

Vanderford, N. L., S. S. Andrali, and S. Özcan. 2007. Glucose induces MafA expression in pancreatic beta cell lines via the hexosamine biosynthetic pathway. J. Biol. Chem. 282: 1577-1584. PMID: 17142462.

Andrali, S. S., Q. Qian and S. Özcan. 2007. Glucose mediates the translocation of NeuroD1 by O-linked glycosylation. J. Biol. Chem. 282:15589-15596. PMID: 17403669.

Andrali, S., Sampley, M. L., Vanderford, N. L., and S. Özcan. 2008. Glucose Regulation of Insulin Gene Expression. Biochem. J. 415:1-10. PMID: 18778246.

Tang, X., L. Muniappan, G. Tang and S. Özcan. 2009. Identification of glucose-regulated miRNAs from pancreatic beta cells reveals a role for miR-30d insulin transcription. RNA. 15:287-293. PMID: 19096044.

Özcan, S., S. S. Andrali, J.E.L. Cantrell. 2010. Modulation of transcription factor function by O-GlcNAc modification. Biochem. Biophys. Acta. 1799:353-364. PMID: 20202486

Sampley, M.L, and S. Özcan. 2012. Regulation of insulin gene transcription by multiple histone acetyltransferases. DNA Cell Biol. 31:8-14. PMID: 21774670

Cantrell Stanford, J., A.J. Morris, M. Sunkara, G.J. Popa, K.L. Larson, and S. Özcan. 2012. Sphingosine 1-Phosphate (S1P) regulates glucose-stimulated insulin secretion in pancreatic beta cells. J. Biol. Chem. 287: 13457-13464. PMID: 22389505.

Zhao, X., R. Mohan, S. Özcan, and X. Tang. 2012. MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase4 (MAP4K4) in pancreatic beta cells. J. Biol. Chem. 287: 31155-31164. PMID: 22733810.

PubMed Publications: 

  • Maganti, A.V.;Maier, B.;Tersey, S.A.;Sampley, M.L.;Mosley, A.L.;Özcan, S.;Pachaiyappan, B.;Woster, P.M.;Hunter, C.S.;Stein, R.;Mirmira, R.G. "Transcriptional activity of the islet β cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9." The Journal of biological chemistry 290, 15 (2015): 9812-22. [PubMed Link] | [ Full text ]
  • Özcan, S. "microRNAs in Pancreatic β-Cell Physiology." Advances in experimental medicine and biology 887, (2015): 101-17. [PubMed Link] | [ Full text ]
  • Niedowicz, D.M.;Reeves, V.L.;Platt, T.L.;Kohler, K.;Beckett, T.L.;Powell, D.K.;Lee, T.L.;Sexton, T.R.;Song, E.S.;Brewer, L.D.;Latimer, C.S.;Kraner, S.D.;Larson, K.L.;Ozcan, S.;Norris, C.M.;Hersh, L.B.;Porter, N.M.;Wilcock, D.M.;Murphy, M.P. "Obesity and diabetes cause cognitive dysfunction in the absence of accelerated β-amyloid deposition in a novel murine model of mixed or vascular dementia." Acta neuropathologica communications 2, (2014): 64. [PubMed Link] | [ Full text ]
  • Ozcan, S. "Minireview: microRNA function in pancreatic β cells." Molecular endocrinology (Baltimore, Md.) 28, 12 (2014): 1922-33. [PubMed Link] | [ Full text ]
  • Zhao, X.;Mohan, R.;Özcan, S.;Tang, X. "MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells." The Journal of biological chemistry 287, 37 (2012): 31155-64. [PubMed Link] | [ Full text ]
  • Sampley, M.L.;Ozcan, S. "Regulation of insulin gene transcription by multiple histone acetyltransferases." DNA and cell biology 31, 1 (2012): 8-14. [PubMed Link] | [ Full text ]
  • Cantrell Stanford, J.;Morris, A.J.;Sunkara, M.;Popa, G.J.;Larson, K.L.;Özcan, S. "Sphingosine 1-phosphate (S1P) regulates glucose-stimulated insulin secretion in pancreatic beta cells." The Journal of biological chemistry 287, 16 (2012): 13457-64. [PubMed Link] | [ Full text ]
  • Ozcan, S.;Andrali, S.S.;Cantrell, J.E. "Modulation of transcription factor function by O-GlcNAc modification." Biochimica et biophysica acta 1799, 5-6 (2010): 353-64. [PubMed Link] | [ Full text ]
  • Ozcan, S. "MiR-30 family and EMT in human fetal pancreatic islets." Islets 1, 3 (2009): 283-5. [PubMed Link] | [ Full text ]
  • Guo, S.;Burnette, R.;Zhao, L.;Vanderford, N.L.;Poitout, V.;Hagman, D.K.;Henderson, E.;Ozcan, S.;Wadzinski, B.E.;Stein, R. "The stability and transactivation potential of the mammalian MafA transcription factor are regulated by serine 65 phosphorylation." The Journal of biological chemistry 284, 2 (2009): 759-65. [PubMed Link] | [ Full text ]
  • Tang, X.;Muniappan, L.;Tang, G.;Ozcan, S. "Identification of glucose-regulated miRNAs from pancreatic beta cells reveals a role for miR-30d in insulin transcription." RNA (New York, N.Y.) 15, 2 (2009): 287-93. [PubMed Link] | [ Full text ]
  • Muniappan, L.;Ozcan, S. "Adenoviral gene transfer into isolated pancreatic islets." Methods in molecular biology (Clifton, N.J.) 590, (2009): 131-42. [PubMed Link] | [ Full text ]
  • Andrali, S.S.;Sampley, M.L.;Vanderford, N.L.;Ozcan, S. "Glucose regulation of insulin gene expression in pancreatic beta-cells." The Biochemical journal 415, 1 (2008): 1-10. [PubMed Link] | [ Full text ]
  • Tang, X.;Tang, G.;Ozcan, S. "Role of microRNAs in diabetes." Biochimica et biophysica acta 1779, 11 (2008): 697-701. [PubMed Link] | [ Full text ]
  • Vanderford, N.L.;Cantrell, J.E.;Popa, G.J.;Ozcan, S. "Multiple kinases regulate mafA expression in the pancreatic beta cell line MIN6." Archives of biochemistry and biophysics 480, 2 (2008): 138-42. [PubMed Link] | [ Full text ]
  • Muniappan, L.;Ozcan, S. "Induction of insulin secretion in engineered liver cells by nitric oxide." BMC physiology 7, (2007): 11. [PubMed Link] | [ Full text ]
  • Andrali, S.S.;Qian, Q.;Ozcan, S. "Glucose mediates the translocation of NeuroD1 by O-linked glycosylation." The Journal of biological chemistry 282, 21 (2007): 15589-96. [PubMed Link] | [ Full text ]
  • Vanderford, N.L.;Andrali, S.S.;Ozcan, S. "Glucose induces MafA expression in pancreatic beta cell lines via the hexosamine biosynthetic pathway." The Journal of biological chemistry 282, 3 (2007): 1577-84. [PubMed Link] | [ Full text ]
  • März, P.;Stetefeld, J.;Bendfeldt, K.;Nitsch, C.;Reinstein, J.;Shoeman, R.L.;Dimitriades-Schmutz, B.;Schwager, M.;Leiser, D.;Ozcan, S.;Otten, U.;Ozbek, S. "Ataxin-10 interacts with O-linked beta-N-acetylglucosamine transferase in the brain." The Journal of biological chemistry 281, 29 (2006): 20263-70. [PubMed Link] | [ Full text ]
  • Andrali, S.S.;März, P.;Ozcan, S. "Ataxin-10 interacts with O-GlcNAc transferase OGT in pancreatic beta cells." Biochemical and biophysical research communications 337, 1 (2005): 149-53. [PubMed Link] | [ Full text ]
  • Finlin, B.S.;Mosley, A.L.;Crump, S.M.;Correll, R.N.;Ozcan, S.;Satin, J.;Andres, D.A. "Regulation of L-type Ca2+ channel activity and insulin secretion by the Rem2 GTPase." The Journal of biological chemistry 280, 51 (2005): 41864-71. [PubMed Link] | [ Full text ]
  • Qian, Q.;Williams, J.P.;Karounos, D.G.;Ozcan, S. "Nitric oxide stimulates insulin release in liver cells expressing human insulin." Biochemical and biophysical research communications 329, 4 (2005): 1329-33. [PubMed Link] | [ Full text ]
  • Mosley, A.L.;Corbett, J.A.;Ozcan, S. "Glucose regulation of insulin gene expression requires the recruitment of p300 by the beta-cell-specific transcription factor Pdx-1." Molecular endocrinology (Baltimore, Md.) 18, 9 (2004): 2279-90. [PubMed Link] | [ Full text ]
  • Mosley, A.L.;Ozcan, S. "The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose." The Journal of biological chemistry 279, 52 (2004): 54241-7. [PubMed Link] | [ Full text ]
  • Lakshmanan, J.;Mosley, A.L.;Ozcan, S. "Repression of transcription by Rgt1 in the absence of glucose requires Std1 and Mth1." Current genetics 44, 1 (2003): 19-25. [PubMed Link] | [ Full text ]
  • Mosley, A.L.;Ozcan, S. "Glucose regulates insulin gene transcription by hyperacetylation of histone h4." The Journal of biological chemistry 278, 22 (2003): 19660-6. [PubMed Link] | [ Full text ]
  • Mosley, A.L.;Lakshmanan, J.;Aryal, B.K.;Ozcan, S. "Glucose-mediated phosphorylation converts the transcription factor Rgt1 from a repressor to an activator." The Journal of biological chemistry 278, 12 (2003): 10322-7. [PubMed Link] | [ Full text ]
  • Lakshmanan, J.;Elmendorf, J.S.;Ozcan, S. "Analysis of insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes." Methods in molecular medicine 83, (2003): 97-103. [PubMed Link] |
  • Mosley, A.L.;Ozcan, S. "Adenoviral gene transfer into beta-cell lines." Methods in molecular medicine 83, (2003): 73-9. [PubMed Link] |
  • Ozcan, S.;Mosley, A.L.;Aryal, B.K. "Functional expression and analysis of the pancreatic transcription factor PDX-1 in yeast." Biochemical and biophysical research communications 295, 3 (2002): 724-9. [PubMed Link] | [ Full text ]
  • Ozcan, S. "Two different signals regulate repression and induction of gene expression by glucose." The Journal of biological chemistry 277, 49 (2002): 46993-7. [PubMed Link] | [ Full text ]