The Glycobiology Laboratory was established in July of 2000. We are interested in understanding the biosynthesis of heparan sulfate polysaccharides and developing an enzymatic approach to synthesize polysaccharide-based therapeutic agents. This laboratory is currently supported by grants from the National Institutes of Health and the American Heart Association.


Our research goal is to develop a novel method to synthesize anticoagulant Heparin drug and antiviral drugs by targeting the biosynthesis of Heparan Sulfate.

Research Articles

  • Michel Weiwer, Trevor Sherwood, Dixy E. Green, Paul L. DeAngelis, Jian Liu, Robert J. Linhardt* (2008) Synthesis of uridine 5’-diphosphoiduronic acid (UDP-IdoA) as a potential unnatural substrate of glucuronosyltransferases for the chemoenzymatic synthesis of heparin. J. Org. Chem. (in press).
  • Zhenqing Zhang, Scott A. McCallum, Jin Xie, Lidia Nieto, Francisco Corzana, Jesús Jiménez-Barbero, Miao Chen, Jian Liu, Robert J. Linhardt* (2008) Solution structures of chemoenzymatically synthesized heparin and its precursors. J. Am. Chem. Soc. (in press).
  • Ronald Copeland, Arun Balasubramaniam, Vaibhav Tiwari, Arleen Bridges, Robert J Linhardt, Deepak Shukla, and Jian Liu* (2008) Using a 3-O-sulfated heparin octasaccharide to inhibit the entry of herpes simplex virus 1 Biochemistry 47: 5774-5783.
  • Xu, D., Moon, A.F., Song, D., Pedersen, L.C. and Liu*, J. (2008) Engineering the sulfotransferases to modify heparan sulfate Nat. Chem. Biol. 4: 200-202.
  • Zhenqing Zhang. Jin Xie, Jian Liu and Robert Linhardt* (2008) Tandem MS can distinguish hyaluronic acid from N-acetylheparosan J. Am. Soc Mass Spect. 19: 82-90
  • Chen, J., Jones, C.L., and Liu*, J. (2007) Using an enzymatic combinatorial approach to identify novel anticoagulant heparan sulfate structures Chemistry & Biology 14: 986-993 (Commentary by Linhardt, R.J. and Kim, J.-H. (2007) Chemistry & Biology 14: 972-973)
  • Xu, D., Song, D., Pedersen, L. and Liu*, J. (2007) Mutational study of heparan sulfate 2-O-sulfotransferase and chondroitin sulfate 2-O-sulfotransferase J. Biol. Chem. 282: 8356-8367.
  • Lawrence, R., Yabe, T., HajMohammadi, S., Rhodes, J., McNeely, M., Liu, J., Lamperti, E.D., Toselli, P.A., Lech, M., Spear, P.G., Rosenberg, R.D., and Shworak*, N.W. (2007) The principal neuronal gD-type 3-O-sulfotrnsferases and their products in central and peripheral nervous system tissues Matrix Biology 26: 442-455.
  • Lu, D., Garcia-Contreras, L., Xu, D., Kurtz, S.L., Liu, J., Braunstein, M., McMurray, D. and Hickey*, A.J. (2007) Poly (Lactide-co-Glycolide) Microspheres Can Enhance a T Cell Response to Recombinant Mycobacterium tuberculosis Antigen 85B. Pharm Res. 24: 1834-1843.
  • Tiwari, V., O’Donnell, C., Copeland, R.J., Scarlett, T., Liu, J. and Shukla* D. (2007) Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells J. Gen Virol. 88: 1075-1079.
  • Chen, M., Bridges, A. and Liu*, J. (2006) Determination of the substrate specificities of N-acetyl-D-glucosaminyl transferase Biochemistry 45: 12358-12365.
  • Vaibhav Tiwari, Christian Clement, Ding Xu, Perry M. Scanlan, Veeral Seth, Gary Chung, Devanand Kowlessur, Tibor Valyi-Nagy, Beatrice Y.J.T. Yue, Jian Liu, and Deepak Shukla* (2006) Entry of HSV-1 into primary cultures of corneal fibroblasts is mediated by HVEM and 3-O-S HS but not nectin-1. J. Virol. 80: 8970-8980.
  • Munoz, E., Xu, D., Kemp, M., Zhang, F., Liu, J., Linhardt*, R.J. (2006) Affinity, kinetic and structural study of the interaction of 3-O-sulfotransferase isoform 1 with heparan sulfate Biochemistry 45: 5122-5128.
  • McDowell, L.M., Frazier, B., Studelska, D.R., Giljum, K., Chen, J., Liu, J., Yu, K., Ornitz, D.M., and Zhang, L.* (2006) Inhibition or activation of Apert syndrome FGFRs (S252W) signaling by specific glycosaminoglycans J. Biol. Chem. 281: 6924-6930.
  • Duncan, M., Liu, M., Fox, C. and Liu, J.* (2006) Characterization of the N-Deacetylase Domain from the Heparan Sulfate N-Deacetylase/N-Sulfotransferase 2 Biochem. Biophys. Res. Commun.339: 1232-1237.
  • Eva Munoz, Ding Xu, Fikri Avci, Melissa Kemp, Jian Liu, Robert J. Linhardt* (2006) Enzymatic synthesis of heparin related polysaccharide on sensor chips: Rapid screening of heparin-protein interactions Biochem. Biophys. Res. Commun. 339:597-602.
  • Jinghua Chen, Fikri Y. Avci, Eva M. Munoz, Lynda M. McDowel, Miao Chen, Lars C. Pedersen, Lijuan Zhang, Robert J. Linhardt, and Jian Liu* (2005) Enzymatic redesigning of biologically active heparan sulfate J. Biol. Chem. 280: 42817-42825.
  • Gong, Y., Duvvuri, M., Duncan, M., Liu, J. and Krise, J.P.* (2006) Niemann-pick C1 protein facilitates the efflux of the anticancer drug duanorubicin from cells according to a novel vesicle-mediated pathway J. Pharmacol. Exp. Ther. 316: 242-247.
  • Jinghua Chen and Jian Liu* (2005) Characterization of the Structure of Antithrombin-binding Heparan Sulfate Generated by Heparan Sulfate 3-O-Sulfotransferase 5 Biochim. Biophys. Acta 1725:190-200.
  • Ding Xu, Vaibhav Tiwari, Guoqing Xia, Christian Clement, Deepak Shukla and Jian Liu* (2005) Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and the role in assisting the entry of herpes simplex virus, type 1. Biochem. J.385: 451-459.
  • Andrea Moon, Suzanne C. Edavettal, Joe M. Krahn, Eva M. Munoz, Masahiko Negishi, Robert J. Linhardt, Jian Liu*, and Lars C. Pedersen (2004) Structural analysis of the sulfotransferase (3-OST-3) involved in the biosynthesis of an entry receptor of herpes simplex virus 1. J. Biol. Chem. 279: 45185-45193 (Cover of October 22 issue).
  • Atsuko Negishi, Jinghua Chen, Douglas McCarty, Jude Samulski, Jian Liu*, and Richard Superfine* (2004) Analysis of the interaction of heparan sulfate and adeno-associated virus by atomic force microscopy. Glycobiology 14: 969-977.
  • Suzanne C. Edavettal, Karen A. Lee, Masahiko Negishi, Robert J. Linhardt, Jian Liu*, and Lars C. Pedersen (2004) Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1. J. Biol. Chem. 279: 25789-25797.
  • Suzanne C. Edavettal, Kevin Carrick, Ruchir Shah, Lars C. Pedersen, Alex Tropsha, R. Marshall Pope, and Jian Liu* (2004) A conformational change of heparan sulfate 3-O-sulfotransferase induced by binding to heparan sulfate. Biochemistry 43: 4680 – 4688.
  • Vaibhav Tiwari, Christain Clement, Michael B. Duncan, Jinghua Chen, Jian Liu, and Deepak Shukla* (2004) A role of 3-O-sulfated heparan sulfate in cell fusion induced by herpes simplex virus type-1. J. Gen. Virol. 85: 805-809.
  • Michael B. Duncan, Jinghua Chen, Jeffrey Krise and Jian Liu* (2004) The contribution of heparan sulfate 3-O-sulfotransferase isoform 5 to the biosynthesis of anticoagulant heparan sulfate. Biochim. Biophys. Acta 1671: 34-43.
  • Jinghua Chen, Michael B. Duncan, Kevin Carrick, R. Marshall Pope, and Jian Liu* (2003) Biosynthesis of 3-O-sulfated heparan sulfate: unique substrate specificity of heparan sulfate 3-O-sulfotransferase isoform 5. Glycobiology 13: 785-794.
  • Guoqing Xia, Jinghua Chen, Vaibhav Tiwari, Wujian Ju, Jing-pin Li, Anders Malmstrom, Deepak Shukla, Jian Liu* (2002) Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus-1. J. Biol. Chem. 277: 37912-37919.
  • Jian Liu*, Zach Shriver, R. Marshall Pope, Suzanne C. Thorp, Michael B. Duncan, Ronald J. Copeland, Christina S. Raska, Keiichi Yoshida, Roselyn J. Eisenberg, Gary Cohen, Robert J. Linhardt, and Ram Sasisekharan (2002) Characterization of a heparan sulfate octasaccharide that binds to herpes simplex viral type 1 glycoprotein D. J. Biol. Chem. 277: 33456-3346.
  • Myette JR, Shriver Z, Liu J, Venkataraman G, Rosenberg R, Sasisekharan R* (2002) Expression in Escherichia coli, purification and kinetic characterization of human heparan sulfate 3-O-sulfotransferase-1. Biochem. Biophys. Res. Commun. 290: 1206-1213.
  • Marshall Pope, Christina S. Raska, Suzanne C. Thorp and Jian Liu* (2001) Analysis of heparan sulfate oligosaccharides by nanoelectrospray ionization mass spectrometry. Glycobiology 11: 505-513.
  • Lijuan Zhang, David L. Beeler, Roger Lawrence, Miroslaw Lech, Jian Liu, Joseph C. Davis, Zachary Shriver, Ram Sasisekharan, and Robert D. Rosenberg (2001) 6-O-Sulfotransferase-1 represents a critical enzyme in the anticoagulant heparan sulfate biosynthetic pathway. J. Biol. Chem. 276: 42311-42321.
  • Maria Hernaiz, Jian Liu, Robert D. Rosenberg, and Robert J. Linhardt (2000) Enzymatic modification of heparan sulfate on a biochip promotes its interaction with antithrombin III. Biochem. Biophys. Res. Commun. 276: 292-297.
  • Deepak Shukla, Jian Liu, Peter Blaiklock, Nicholas W. Shworak, Xiaomei Bai, Jeffrey D. Esko, Gary H. Cohen, Roselyn J. Eisenberg, Robert D. Rosenberg and Patricia G. Spear (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99: 13-22.(Both authors contributed equally to this work.)
  • Jian Liu, Zach Shriver, Peter Blaiklock, Keiichi Yoshida, Ram Sasisekharan, and Robert D. Rosenberg (1999) Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3A sulfates N-unsubstituted glucosamine. J. Biol. Chem. 274: 38155-38162.
  • Jian Liu, Nicholas W. Shworak, Pierre Sinay, John J. Schwartz, Lijuan Zhang, Linda M.S. Fritze and Robert D. Rosenberg (1999) Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities. J. Biol. Chem. 274: 5185-5192.
  • Nicholas W. Shworak, Jian Liu, Lorin M. Petros, Neal G. Copeland, Nancy A. Jenkins and Robert D. Rosenberg (1999) Diversity of the extensive heparan sulfate D-glucosaminyl 3-O-sulfotransferase (3-OST) multigene family. J. Biol. Chem. 274: 5170-5184.
  • Lijuan Zhang, Keiichi Yoshida, Jian Liu and Robert D. Rosenberg (1999) Anticoagulant heparan sulfate precursor structures in F9 embryonic carcinoma cells. J. Biol. Chem. 274: 5681-5691.
  • Masashi Kobayashi, Geetha Sugumaran, Jian Liu, Nicholas W. Shworak, Jeremiah E. Silbert, and Robert D. Rosenberg (1999) Molecular cloning and characterization of a human uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate. J. Biol. Chem. 274: 10474-10480.
  • Lijuan Zhang, John J. Schwartz, Joseph Miller, Jian Liu, Linda M.S.Fritze, Nicholas W. Shworak, Robert D. Rosenberg (1998) The retinoic acid and cAMP-dependent up-regulation of 3-O-sulfotransferase-1 leads to a dramatic augmentation of anticoagulantly active heparan sulfate biosynthesis in F9 embryonal carcinoma cells. J. Biol. Chem. 273: 27998-28003.
  • Nicholas W. Shworak, Jian Liu, Linda M.S. Fritze, John J. Schwartz, Lijuan Zhang, Logear, D. and Robert D. Rosenberg (1997) Molecular cloning and expression of mouse and human cDNAs encoding heparan sulfate D-glucosaminyl 3-O-sulfotransferase. J. Biol. Chem. 272: 28008-28019.
  • Jian Liu, Nicholas W. Shworak, Linda M.S. Fritze, Jay M. Edelberg and Robert D. Rosenberg (1996) Purification of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. J. Biol. Chem. 271: 27072-27082.
  • Nicholas W. Shworak, Linda M.S. Fritze, Jian Liu, Lynne D. Butler and Robert D. Rosenberg (1996) Cell-free synthesis of anticoagulant heparan sulfate reveals a limiting converting activity that modifies an excess precursor pool. J. Biol. Chem. 271: 27063-27071.
  • Ghamartaj Hossein, Jian Liu and Ariane I. De Agostini (1996) Characterization and hormonal modulation of anticoagulant heparan sulfate proteoglycans synthesized by rat ovarian granulosa cells. J. Biol. Chem. 271: 22090-22099.
  • Jian Liu, Umesh R. Desai, Xue-Jun Han, Toshihiko Toida and Robert J. Linhardt (1995) Strategy for the sequence analysis of heparin. Glycobiology 5: 765-774.
  • Sylvia Colliec-Jouault, Nicholas W. Shworak, Jian Liu, Ariane I. De Agostini and Robert D. Rosenberg (1994) Characterization of a cell mutant specifically defective in the synthesis of anticoagulantly active heparan sulfate. J. Biol. Chem. 271: 24953-24958.
  • Nicholas W. Shworak, Motoaki Shirakawa, Sylvia Colliec-Jouault, Jian Liu, Richard C. Mulligan, Louis K. Birinyi and Robert D. Rosenberg (1994) Pathway-specific regulation of the biosynthesis of anticoagulantly active heparan sulfate. J. Biol. Chem. 269: 24941-24952.
  • Y. S. Kim, J. Liu, X.J. Han, A. Pervin and R. J. Linhardt (1994) Analysis of fluorescently labeled sugars by reversed-phase ion-pairing high performance liquid chromatography. J. Chromatogr. Sci. 33: 162-167.
  • Jian Liu, Azra Pervin, Cindy M. Gallo, Umesh R. Desai, Case VanGorp and Robert J. Linhardt (1994) New approaches for the preparation of hydrophobic heparin. J. Pharmaceut. Sci. 83: 1034-1039.
  • Robert J. Linhardt, Umesh Desai, Jian Liu, Debra Hoppensteadt and Jawed Fareed (1994) Low molecular weight dermatan sulfate as an antithrombotic agent: Structure activity relationship studies. Biochem. Pharmacol. 47: 1241-1252.
  • Kenan Gu, Jian Liu, Azra Pervin and Robert J. Linhardt (1993) Comparison of the activity of two chondroitin AC lyases on dermatan sulfate. Carbohydr. Res. 244: 369-377.
  • Robert J. Linhardt, Ali Al-Hakim, Jian Liu, Debra Hoppensteadt, Jawed Fareed, Guiseppe Mascellani, and Pietro Bianchini (1991) Structure features of dermatan sulfates and their relationship to anticoagulant and antithrombotic activities. Biochem. Pharmacol. 42: 1609-1619.
  • Youhan Xu, Jian Liu, Suipo Zhang and Lisheng Liu (1987) The effect of berbamine derivatives on activated Ca2+-stimulated Mg2+-dependent ATPase in erythrocyte membranes. Biochem. J. 248: 985-988.
  • Fayi Zhang, Yibao Zhang, Jian Liu and Xuezhuang Zhao (1986) Ascorbic acid oxidation reaction-kinetics of oxidation by molecular oxygen. WuliHuaxue Xuebao 2: 335-341 (in Chinese).

Peer-Reviewed Articles

  • Robert J Linhardt*, Jonathan S. Dordick, Paul DeAngelis, Jian Liu (2007) Enzymatic synthesis of glycosaminoglycan heparin Semin. Thromb. Hemost. 33: 453-465.
  • Jian Liu* and Lars C. Pedersen (2007) Anticoagulant heparan sulfate: Structural specificity and biosynthesis. Appl. Microbiol. Biotechnol. 74:263-272.
  • Jian Liu* and Suzanne C. Thorp (2001) Cell surface heparan sulfate and the roles in assisting viral infections. Med. Res. Rev. 22:1-25.
  • Robert D. Rosenberg*, Nicholas W. Shworak, Jian Liu, John J. Schwartz, and Lijuan Zhang (1997) Heparan sulfate proteoglycans of the cardiovascular system: specific structures emerge but how is synthesis regulated J. Clin. Invest. 99: 2062-2070.
  • Robert J. Linhardt*, Jian Liu and Xue-jun Han (1993) Mapping and sequencing of oligosaccharides by electrophoresis. Trends Glycosci. Glycotechnol. 5: 181-192.

Refereed Book Chapters

  • Fikri Y. Avci, Paul L. DeAngelis, Jian Liu, and Robert J. Linhardt* (2007) Enzymatic synthesis of glycosaminoglycans: improving on nature, in Frontiers in Carbohydrate Chemistry, pp 253-284.
  • Jian Liu* and Robert D. Rosenberg (2001) Heparan sulfate D-glucosaminyl 3-O-sulfotransferase, in Handbook of Glycosyltransferases and Their Related Genes (N. Taniguchi and M. Fukuda Eds.) Springer-Verlag, Tokyo pp 475-483. (Book Chapter)
  • Robert J. Linhardt*, Ali Al-Hakim and Jian Liu (1991) Acidic polysaccharides: Their modification and potential uses, in Biotechnology and Polymers (C. G. Gebelein Ed.) Plenum Press, new York, 155-165. (Book Chapter)

Jian Liu, Ph.D.

(919) 843-6511 liuj@email.unc.edu

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.

Qisheng Zhang, Ph.D.

(919) 966-9687 qszhang@email.unc.edu

The Zhang lab studies lipid signaling pathways that are involved in development and diseases by developing novel chemical probes and technologies. As key components of cellular membranes, lipids also serve as signaling molecules and modify functions of proteins through either covalent or non-covalent interactions.

Non-UNC Eshelman School of Pharmacy Collaborations

Robert J. Linhardt, PhD


(518) 276-3404

Lars C. Pedersen, PhD


(919) 541-0444

Deepak Shukla, PhD


(312) 355-0908

Gowthami M. Arepally, MD

(919) 668-3696

Huang Xuefei


(517) 355-9715

Heather Bethea, PhD


Kai Li, PhD


Renpeng Liu, PhD


Juzheng Sheng, PhD


Xianxuan Zhou, PhD