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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. |