This Center is dedicated to the development of technologies and tools for the identification and characterization of glycan structures and transcripts associated with cellular glycoproteins and glycolipids. As a test-bed for the further development of glycomic technologies and tools, studies will again focus on the characterization of human pluripotent stem cells, including embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). A range of differentiated cell lineages derived from stem cells will be incorporated into this analysis. This biological model is ideal as a test-bed for glycomics technologies and tool development because it offers a diverse range of glycan structures and challenges due to the diversity in cell types that can be generated. These studies will offer new insights into human embryonic development and will lead to the identification of new biomarkers for stem cell characterization. A major strength of this TR&D has been its success in generating pure, well-characterized cell types from hESC and hiPSCs. For example, we routinely produce neural, liver, pancreatic and cardiac lineages that are suitable for downstream analysis. The first method for direct differentiation of neural crest stem cells from pluripotent cells [1] was developed as part of the Center's previous round of funding. Additional cardiovascular lineages are also being developed to increase the diversity of cells to be analyzed by other TR&Ds'and to enhance glycan complexity that will be encountered. In this competitive renewal, we propose to extend our previous work and also include a new emphasis on human iPSC models for glycosylation-related disease. Understanding the basis of these diseases represents a major challenge and an area that is largely underexplored and poorly understood. Using iPSC-reprogramming technology, we propose to generate panels of fully validated cell lines that can serve as models for human congenital disorders of glycosylation (CDG) and congenital muscular dystrophy (CMD). This will serve to provide valuable resources for a large number of investigators and to create a truly challenging test-bed for glycomics technology development. Another major new component of this TR&D is the inclusion of Dr. Richard Steet as co-investigator. Dr. Steet will bring his broad expertise in the area of congenital glycosylation disorders to this effort and will be primarily responsible for the biochemical validation of the resulting cell lines. Dr. Steet will also coordinate the interactions between many DBP collaborators and personnel within this TR&D.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
2P41GM103490-11
Application #
8529766
Study Section
Special Emphasis Panel (ZRG1-IMST-J (40))
Project Start
Project End
2018-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
11
Fiscal Year
2013
Total Cost
$2,859,327
Indirect Cost
$622,334
Name
University of Georgia
Department
Type
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Talabnin, Krajang; Talabnin, Chutima; Ishihara, Mayumi et al. (2016) Differential Expression of O-glycoprotein Glycans in Cholangiocarcinoma Cell Lines. Asian Pac J Cancer Prev 17:691-5
Yu, Seok-Ho; Zhao, Peng; Sun, Tiantian et al. (2016) Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. J Biol Chem 291:3982-9
Parkinson, William M; Dookwah, Michelle; Dear, Mary Lynn et al. (2016) Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model. Dis Model Mech 9:513-27
Berger, Ryan P; Dookwah, Michelle; Steet, Richard et al. (2016) Glycosylation and stem cells: Regulatory roles and application of iPSCs in the study of glycosylation-related disorders. Bioessays 38:1255-1265
Deligny, Audrey; Dierker, Tabea; Dagälv, Anders et al. (2016) NDST2 (N-Deacetylase/N-Sulfotransferase-2) Enzyme Regulates Heparan Sulfate Chain Length. J Biol Chem 291:18600-7
Durning, Sean P; Flanagan-Steet, Heather; Prasad, Nripesh et al. (2016) O-Linked β-N-acetylglucosamine (O-GlcNAc) Acts as a Glucose Sensor to Epigenetically Regulate the Insulin Gene in Pancreatic Beta Cells. J Biol Chem 291:2107-18
Sanda, Miloslav; Benicky, Julius; Wu, Jing et al. (2016) Increased sialylation of site specific O-glycoforms of hemopexin in liver disease. Clin Proteomics 13:24
LaMattina, Joseph W; Nix, David B; Lanzilotta, William Nicholas (2016) Radical new paradigm for heme degradation in Escherichia coli O157:H7. Proc Natl Acad Sci U S A 113:12138-12143
Hildebrandt, Emily R; Cheng, Michael; Zhao, Peng et al. (2016) A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes. Elife 5:
Aoki-Kinoshita, Kiyoko; Agravat, Sanjay; Aoki, Nobuyuki P et al. (2016) GlyTouCan 1.0 - The international glycan structure repository. Nucleic Acids Res 44:D1237-42

Showing the most recent 10 out of 76 publications