Research Synopsis

Identification of polysaccharide-based receptor; structure and specificity of a heparan sulfate-based herpes simplex virus 1 receptor; drug targeting; gene therapy.

Research Profile

Research in the Jian Liu group is focused on glycobiology and glycobiochemistry, an emerging field that emphasizes the biological functions of carbohydrates. We are particularly interested in understanding the biosynthetic mechanism of sulfated polysaccharides known as heparan sulfate and heparin.

Heparan sulfate is found on the cell surface and in the extracellular matrix in large quantities. Heparan sulfate is involved in a wide range of biological functions, including regulating blood coagulation, controlling embryonic development, and resisting viral infections. We also study the biosynthesis of heparin, a polysaccharide that has similar structure to heparan sulfate. Heparin is a widely used anticoagulant drug with more than $4 billion dollars in worldwide annual sales.

In addition to understand the biosynthesis of heparan sulfate, we are also in the process of developing an enzyme- or chemoenzyme-based method to synthesize heparin. Heparin is currently isolated from animal sources, and its supply chain can be vulnerable to contamination. The chemoenzymatic method should significantly simplify the preparation of heparin and ultra-low molecular weight heparin. This method has great potential to synthesize a cheaper, cleaner, and safer heparin drug.

The research group, consisting of postdoctoral fellows, graduate students, and pharmacy students, is actively pursuing different aspects of the biochemistry of heparin and heparan sulfate. These individuals have expertise in chemistry, biochemistry, molecular biology, and microbiology. The research group is funded by grants from the National Institutes of Health and the American Heart Association. Further detailed information about our research can be found in our publications.

Ten Most Recent Publications

1. Chemoenzymatic synthesis of heparan sulfate oligosaccharides with anti-IIa activity.

Yongmei Xu, Elizabeth H. Pempe, and Jian Liu* (2012)  Submitted.

2. Substrate specificity of 6-O-endosulfatase isoform 2 and its implications in synthesizing anticoagulant heparan sulfate. Elizabeth H. Pempe, Tanya C. Burch, Courtney J. Law and Jian Liu* (2011) Submitted.

3. Probing the structural selectivity of synthetic heparin binding to stabilin receptors. Elizabeth H. Pempe,Yongmei Xu, Sandhya Gopalakrishnan, Jian Liu, Edward N. Harris^* (2011) Submitted.

4. Unveiling substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin. Moon, A., Xu, Y., Woody, S.M., Krahn, J.M., Linhardt, R.J., Liu*, J. and Pedersen, L.C., (2011) Submitted.

5. Directing the biological activities of heparan sulfate oligosaccharides using a chemoenzymatic approach. Xu, Y., Wang, Z., Liu, R., Arlene Bridges, Huang*, X., and Liu, J.* (2012) Glycobiology 22:  96-106.

6. Anti-heparan sulfate peptides that block herpes simplex virus infection in vivo. Tiwari, V., Liu, J., Valyi-Nagy, T., and Shukla*, D. (2011) J. Biol. Chem. 286: 25406-25415.

7. Control of the heparosan N-deacetylation leads to an improved bioengineered heparin. Wang, Z., Yang, B., Zhang, Z., Ly, M., Takeiddin, M., Mousa, S., Liu, J., Dordick, J.S., Linhardt*, R.J. (2011)  Appl. Microbiol. Biotechnol. 91: 91-99.

8. The dominating role of N-deacetylase/N-sulfotransferase 1 in forming domain structures in heparan sulfate. Sheng, J., Liu, R., Xu, Y. and Liu*, J. (2011) J Biol. Chem. 286: 19768-19776.

9. Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins. Xu, Y., Masuko, S., Takieddin, M., Xu, E., Liu, R., Jing, J., Mousa, S., Linhardt*, R.J. and Liu*, J. (2011)  Science 334: 498-501. (Perspective article by Turnbull, J.E. (2011) Getting the farm out of pharma for heparin production Science 334:462-463)

10. Enzymatic placement of 6-O-sulfo groups in heparan sulfate. Liu, R. and Liu*, J. (2011) Biochemistry 50:4382-4391.