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jian_liu

Jian Liu

John & Deborah McNeill, Jr. Dist Prof

Jian Liu, Ph.D.

John & Deborah McNeill, Jr. Distinguished Professor, Division of Chemical Biology and Medicinal Chemistry


jian_liu

PHONE
(919) 843-6511
EMAIL
liuj@email.unc.edu
ADDRESS
1044 Genetic Medicine Bldg, , CB# 7356, Chapel Hill, NC, 27599-7568
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ACCEPTING DOCTORAL STUDENTS

 

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.

  1. He, W., Zhu, Y., Shirke, A., Sun, X., Liu, J., Gross, R.A., Koffas*, M.A.G., Linhardt*, R.J., and Li*, M. (2017) Expression of chondroitin-4-sulfotransferase in Escherichia Coli and Pichia pastoris Appl. Microbiol. Biotechnol., accepted.
  2. Meneghetti, M.C.Z., Ferreira, T.G., Tashima, A.K., Chavante, S.F., Yates, E.A., Liu, J., Nader, H.B., and Lima*, M.A. (2017) Insights into the role of 3-O-sulfotransferase in heparan sulfate biosynthesis Org. Biomol. Chem., accepted.
  3. Xu, Y., Chandarajoti, K., Zhang, X., Pagadala, V., Dou, W., Hoppensteadt, D.M., Sparkenbaugh, E., Colley, B., Daily, S., Key, N., Severynse-Stevens, D., Fareed, J., Linhardt*, R.J., Pawlinksi*, R., and Liu*, J. (2017) Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins Sci Transl. Med., 9, eaan5954.
  4. Nam, E.J., Hayashida, K., Aquino, R.S., Couchman, J.R., Kozar, R.A., Liu, J. and Park*, P.W. (2017) Syndecan-1 limits the progression of liver injury and promotes liver repair in acetaminophen-induced liver injury Hepatology, accepted.
  5. Arnold, K.M., Capuzzi, S.J., Xu, Y., Muratov, E.N., Carrick, K., Szajek, A.Y., Tropsha, A., and Liu*, J. (2017) Modernization of enoxaparin molecular weight determination using homogeneous standards Pharmaceuticals, accepted.
  6. Li, J., Su, G. and Liu*, (2017) Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides Angew. Chem. Int. Ed, accepted.
  7. Pollet, R.M., D’Agostino, E.H., Walton, W.G., Xu, Y., Little, M.S., Biernat, K.A., Pellock, S.J., Patterson, L.M., Creekmore, B.C., Isenberg, H.N., Bahethi, R.R., Bhatt, A.P., Liu, J., Gharaibeh, R.Z., Redinbo, M.R. (2017) An atlas of β-glucuronidase in the human intestinal microbiome Structure, accepted.
  8. Sommers*, C.D., Ye, H., Liu, J., Linhardt, R.J., Keire, D.A. (2017) heparin and homogeneous model heparin oligosaccharides form distinct complexes with protamine: Light scattering and zeta potential analysis J. Pharmaceut. Biomed. Anal. Accepted.
  9. Wang, Z., Hsieh, P-H., Xu, Y., Thieker, D., Chai, E.J.E., Xie, S., Colley, Woods, R.J., Chi, L., Liu*, J. (2017) Synthesis of 3-O-sulfated oligosaccharides to understand the relationship between structures and functions of heparan sulfate J. Am. Chem. Soc., 139: 5249-5256.
  10. Schultz, V., Suflita, M., Liu, X., Zhang, X., Yu, Y., Li, L., Green, D.E., Xu, Y., Zhang, F. DeAngelis, P.L., Liu, J, Linhardt*, R.J. (2017) Heparan sulfate domains required for fibroblast growth factor 1 and 2 signaling through fibroblast growth factor receptor 1c J. Biol. Chem.  doi/10.1074/jbc.M116.761585.

 


  • 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