Jian Liu, PhD

John & Deborah McNeill, Jr. Dist Prof Professor

Research

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.

National Institute of Allergy/Infectious Diseases, 2R01AI050050-05A1, February 1 of 2006 to January 31 of 2011.  Project title: “Structural specificity of heparan sulfate for herpes infection” (Principal Investigator).  Direct cost $226,000/yr for five years, 15% effort.

National Heart, Lung and Blood Institute. 1R01HL094463-01, February 13 of 2009 to January 31 of 2013.  Project title: “In vitro synthesis of recombinant heparan sulfate” (Principal Investigator).  Direct cost $286,000/yr for 4 years, 15% effort.

National Institute of Allergy/Infectious Diseases, 3R01AI050050-07S1, February 1 of 2008 to January 31 of 2011.  Project title: “Structural specificity of heparan sulfate for herpes infection” (Principal Investigator).  Direct cost $33,000/yr for three years.  This grant is to support Ms. Courtney Jones’ PhD studies.

National Heart, Lung, and Blood Institute, 3R01HL094463-01S1, July 1 of 2009 to January 31 of 2013.  Project title: “In vitro synthesis of recombinant heparan sulfate” (Principal Investigator).  Direct cost $33,961/yr.  This grant is to support Ms. Priscilla Paul’s PhD studies.

National Institute of Allergy/Infectious Diseases, 1R21AI074775-01A2, August 1 of 2009 to July 31 of 2011.  Project title: “Glycomics of Heparan Sulfate in Bacterial Pathogenesis” (Principal Investigator).  Direct cost, $150,000/yr1 and $125,000/yr2, 10% effort.

National Heart, Lung and Blood Institute. 1R01HL096972-01, August 1 of 2009 to April 30 of 2014.  Project title: “Development of a Bioengineered Heparin from a Non-Animal Source” (Principal Investigator, Robert J Linhardt).  Role in the project: Co-PI.  Direct cost $100,000/yr for Yr 1-Yr3 and $75,000/yr for Yr4-Yr5, 5% effort.

National Institute of Allergy/Infectious Diseases, 3R01AI050050, September 18 of 2009 to August 31 of 2010.  Project title: “Structural specificity of heparan sulfate for herpes infection” (Principal Investigator).  Direct cost $99,760.  This grant is to purchase a LC/MS system.

National Institute of General Medical Sciences, 1R01GM090257-01, September 30 of 2009 to August 31 of 2011.  Project title: “An artificial Golgi: Controlled GAG synthesis and screening” (Principal Investigator, Robert J Linhardt).  Role in the project: Co-PI.  Direct cost $55,000/yr1 and $65,000/yr 2, 3% effort.

National Institute of Allergy/Infectious Diseases, 3R01AI50050-9S1, May 17 of 2009 to September 30 of 2010.  Project title: “Structural specificity of heparan sulfate for herpes infection” (Principal Investigator).  Direct cost $5,029.  This grant is to support the summer research training for Mrinalini Ramanan.

National Institute of General Medical Sciences, 1R01GM072667-06, June 1 of 2010 to May 30 of 2014.  Project title: “Chemoenzymatic synthesis of heparan sulfate oligosaccharides- subcontract” (Principal Investigator, Xuefei Huang).  Role in the project: Co-PI.  Direct cost $60,000/yr for four years, 4% effort.

National Institute of General Medical Sciences, 1R01GM093131-01, May 1 of 2010 to April 30 of 2014.  Project title: “STRUCTURE AND FUNCTION OF 3-O-SULFATION IN HEPARAN SULFATE” (Principal Investigator, Jeff Esko).  Role in the project: Co-PI.  Direct cost $16,000/yr for two years, 3% effort.

National Science Foundation, CHE-1111550, July 1 of 2011 to June 30 of 2014.  Project title: “Synthesis of homogeneous heparan sulfate proteoglycans” (Principal Investigator, Xuefei Huang).  Role in the project: Co-PI.  Direct cost $29,000/yr for three years, 3% effort.

Education, Certification and Licensure

  • 1993 to 1999 Postdoctoral Research Associate
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA
    Mentor: Professor Robert D. Rosenberg
  • 1989 to 1993 PhD in Medicinal Chemistry and Natural Products
    College of Pharmacy, University of Iowa, Iowa City, Iowa
    Thesis Adviser: Professor Robert J. Linhardt
  • 1984 to 1987 MS in Biochemistry, Nankai University, Tianjin, China
  • 1980 to 1984 BS in Chemistry, Nankai University, Tianjin, China

Publications

  • Chemoenzymatic synthesis of heparan sulfate oligosaccharides with anti-IIa activity. Yongmei Xu, Elizabeth H. Pempe, and Jian Liu* (2012).
  • 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.
  • 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).
  • Probing the structural selectivity of synthetic heparin binding to stabilin receptors. Elizabeth H. Pempe,Yongmei Xu, Sandhya Gopalakrishnan, Jian Liu, Edward N. Harris* (2011).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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)
  • Enzymatic placement of 6-O-sulfo groups in heparan sulfate. Liu, R. andLiu*, J. (2011) Biochemistry 50:4382-4391.