xxx

Sabire Ozcan

Associate Professor
B.S. /M.S Heinrich-Heine University, Duesseldorf, Germany
Ph.D. Heinrich-Heine University, Duesseldorf, Germany
Postdoc. Washington University, St. Louis, Missouri
sozcan@uky.edu
859-257-4821

Research Interests  |  Publications  |  Lab  |  PubMed 

Research Interests:

Our laboratory studies the biological effects of glucose on metabolism, glucose transport, and regulation of gene expression in eukaryotic organisms such as yeast and mammals. Understanding the mechanisms by which glucose induces gene expression is important, since defect in this process result in metabolic disorders such as diabetes mellitus, which affects over 8% of the American population. The major projects in the laboratory are:

1. Analysis of the mechanisms leading to glucose-stimulated insulin gene transcription in pancreatic beta cells and identification of the components of this glucose signaling pathway. We have recently discovered that high blood glucose levels induce insulin gene expression by hyperacetylation of histone H4 at the insulin gene promoter via the recruitment of co-activators. Understanding the mechanisms by which increases in blood glucose levels stimulate insulin gene expression in the pancreas will contribute to the design of novel clinical interventions to treat type I and type II diabetes.

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 such as 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. We are interested in studying the role of O-linked GlcNAc modification in regulation of gene expression in the insulin producing pancreatic beta cells.

3. Engineering of non-beta cells to produce insulin in a glucose-regulated manner. Currently, there is a high demand for insulin producing non beta cells as a treatment for type I as well as type II diabetes. We were able to utilize liver cells for production of insulin by introducing beta cell specific transcription factors or the human insulin cDNA and are interested in exploring stem cells for insulin production.

In summary, the information obtained in pursuit of these projects should significantly advance our understanding of how glucose effects metabolism, transport, and gene transcription in pancreatic beta cells. This will provide new insights into the mechanisms underlying metabolic disorders such as Diabetes and should enable the development of new strategies for the treatment and prevention of such diseases.
 

Representative Publications: 

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

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.  

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. 

Finlin, B. S., A. L. Mosley, S. M. Crump, R. N. Correll, S. Özcan, J. Satin, and D. A. Andres. 2005. Regulation of L-type Ca²⁺ channel activity and insulin secretion by the Rem2 GTPase. J. Biol. Chem. 280:41863-41871. 

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. 

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. 

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