Kuberan Balagurunathan

Professor

Office:

Phone: 801.587.9474
Fax: 801.585.6208

Education:

Post-Doctoral Training 2001-2004 MIT
Ph.D. 2000 University of Iowa
M.S. 1994 Indian Institute of Technology Madras


Research Interests

HEPARAN SULFATE PROTEOGLYCANS: Biosynthesis, Structures and Functions

In the post-genomics era, it is now accepted that complex glycoconjugates such as proteoglycan regulate numerous patho-physiological processes in all living species.  They carry enormous structural information in terms of sulfation, epimerization, domain organization, chain length, number of chains and type of chains along with their core proteins.   Production of proteoglycans with such high complexity occurs in template-independent fashion seamlessly, yet our understanding of their biosynthesis, structures and functions is somewhat incomplete and imperfect.   We are developing a wide variety of chemical biology tools to define the biosynthetic pathways of heparan sulfate and related glycosaminoglycans (GAG) such as chondroitin sulfate and dermatan sulfate.  We synthesize heparin and heparan sulfate structures with a dozen recombinant enzymes to define the structural basis for the interactions of growth factors and Heparan sulfates and the subsequent biological actions.  We recently found that a library of click-xylosides produce distinct GAG chains in cellular systems and proposed a GAGOSOME model for the dynamic regulation of combinatorial GAG biosynthesis.   These molecular tools are currently used in the lab to define the snap shots of biosynthetic events and signaling events that are associated with development and diseases with a final goal to advance the study of heparanomics.


Related Links

Kuby's Laboratory Website

Visit Kuby's Laboratory Website


Publications

Peer-Reviewed Publications and Book Chapters

“Discovery of novel sulfonated small molecules that inhibit vascular tube formation”, K. Raman, R. Karuturi, V.P. Swarup, U.R. Desai, B. Kuberan, Bioorg Med Chem Lett, 22, 4467-4470, 2012

“A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of D-glucosaminyl 3-O-sulfotransferase-3a”, T. K. Nguyen, S. Arungundram, V.M. Tran, K. Raman, K. Al-Mafraji, A. Venot, G. J. Boons, B. Kuberan, Mol Biosyst, 8, 609-614, 2012

” Is N-sulfation just a gateway modification during heparan sulfate biosynthesis?”, Karthik Raman, Thao Kim Nu Nguyen, B. Kuberan, FEBS Letters, 585, 3420-3423, 2011

“Investigating the Mechanism of the Assembly of FGF1-binding heparan sulfate motifs”, Thao Kim Nu Nguyen, Karthik Raman, Vy My Tran, B. Kuberan, FEBS Letters, 585, 2698-2702, 2011

“Novel Glycosaminoglycan Biosynthetic Inhibitors Affect Tumor-associated Angiogenesis”, Karthik Raman, Ninomiya, Thao K. N. Nguyen, Yasuhiro Tsuzuki, Mamoru Koketsu, B. Kuberan, Biochemical and Biophysical Research Communications, 404, 86-89, 2011

“Applications of Isotopes in Advancing Structural and Functional Heparanomics”, Vy M. Tran, Thao K. N. Nguyen, Karthik Raman, B. Kuberan, Analytical and Bioanalytical Chemistry, 399, 559-570, 2011

“4-Deoxy-4-fluoro-xyloside derivatives as Inhibitors of Glycosaminoglycan Biosynthesis”, Yasuhiro Tsuzuki*, Thao K. N. Nguyen*, Dinesh R. Garud, B. Kuberan, Mamoru Koketsu, Bioorganic & Medicinal Chemistry Letters, 20, 7269-7273, 2010 [*authors contributed equally]

“Differential Effects of Heparitinase I and Heparitinase III on Endothelial Cell Tube Formation In vitro”, Karthik Raman and B. Kuberan, Biochemical and Biophysical Research Communications, 398, 191-193, 2010

“Click-Xylosides Mitigate Glioma Invasion In vitro”, Karthik Raman and B. Kuberan, Molecular BioSystems, 6, 1800-1802, 2010

“Hydrogen/Deuterium Exchange-LC-MS Approach to Characterize the Action of Heparan Sulfate C5-Epimerase”, Ponnusamy Babu, Xylophone Victor, Emily Nelson, Thao K. N. Nguyen, Karthik Raman, B. Kuberan, Analytical and Bioanalytical Chemistry, 401, 237-244, 2011

“Characterization of Uniformly and Atom-Specially 13C-Labeled Heparin and Heparan Sulfate Polysaccharide Precursors using 13C-NMR Spectroscopy and ESI-Mass Spectrometry”, Thao K. N. Nguyen, Vy M. Tran, Xylophone Victor, Jack Skalicky, B. Kuberan, Carbohydrate Research, 345, 2228-2232, 2010

“RGD-Xyloside Conjugates Prime Glycosminoglycans”, Vy M. Tran, Xylophone V. Victor, James Yockman, B. Kuberan, Glycoconjugate Journal, 6, 625-633, 2010

“Preparation and Characterization of 15N-Enriched, Size-defined Heparan Sulfate Precursor Oligosaccharides”, Crystal Sigulinsky, Ponnusamy Babu, Xylophone V. Victor and B. Kuberan, Carbohydrate Research, 345, 250-256, 2010

“Chemical Tumor Biology of Heparan Sulfate Proteoglycans”, Current Chemical Biology, Karthik Raman, B. Kuberan, Current Chemical Biology, 4, 20-31, 2010

“Fluorescent Tagged Heparan Sulfate Precursor Oligosaccharides to Probe the Enzymatic Action of Heparitinase I”, P. Babu and B. Kuberan, Analytical Biochemistry, 396, 124-132, 2010

“Investigating the Elusive Mechanism of Glycosaminoglycan Biosynthesis”, Xylophone V. Victor, Thao K. N. Nguyen, Manivannan Ethirajan, Vy M. Tran, Khiem V. Nguyen and B. Kuberan, Journal of Biological Chemistry, 284, 25842-25853, 2009

“Inhibition of Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis”, Dinesh R. Garud*, Vy M. Tran*, Xylophone V. Victor, Mamoru Koketsu, B. Kuberan, Journal of Biological Chemistry, 283, 28881-28887, 2008 [*authors contributed equally]

“Click”- Xylosides Initiate Glycosaminoglycan Biosynthesis in a Mammalian Cell line”, B. Kuberan, Manivannan Ethirajan, Xylophone Victor, Vy M Tran, Khiem V Nguyen and Anh Do, ChemBioChem, 9, 198 - 200, 2008

“Splenic Proteoglycans of Amyloid-Susceptible and Amyloid-Resistant Mice. 1. Quantitation and Characterization of Glycosaminoglycans Accumulated In Vivo after Induction for Amyloid Formation”, G. Sugumaran, R. Elliott-Bryant, N. Phung, O. Vitseva, M. Lech, B. Kuberan, Scandinavian Journal of Immunology, 60 (6), 574-583, 2004

“Light Induced 3-O-Sulfotransferase Expression Alters Pineal Heparan Sulfate Fine Structure: A Surprising Link to Circadian Rhythm”, B. Kuberan, M. Lech, J. Borjigin, R. D. Rosenberg, Journal of Biological Chemistry, 279 (7), 5053-5054, 2004

“Mapping Critical Biological Motifs and Biosynthetic Pathways of Heparan Sulfate”, R. Lawrence, B. Kuberan, M. Lech, D. L. Beeler, R. D. Rosenberg, Glycobiology, 14 (5), 467-479, 2004

“Chemoenzymatic Synthesis of Classical and Non-classical Anticoagulant Heparan Sulfate Polysaccharides”, B. Kuberan, D. L. Beeler, M. Lech, Z. L. Wu, R. D. Rosenberg, Journal of Biological Chemistry, 278 (52), 52613-52621, 2003

“Rapid Two Step Synthesis of Mitrin from Heparosan: A Replacement for Heparin”, B. Kuberan, D. L. Beeler, R. Lawrence, M. Lech, R. D. Rosenberg, Journal of the American Chemical Society, 125 (41), 12424-12425, 2003

“Enzymatic Synthesis of Antithrombin III Binding Heparan Sulfate Pentasaccharide”, B. Kuberan, D. L. Beeler, M. Lech, Z. L. Wu, R. D. Rosenberg, Nature Biotechnology, 21 (11), 1343-1346, 2003

“Synthesis of a C - Glycoside Analogue of sTn: An HIV and Tumor Associated Antigen”, B. Kuberan, S. A Sikkander, H. Tomiyama, R. J. Linhardt, Angewandte Chemie-International Edition, 42 (18), 2073-2075, 2003

“The Involvement of Heparan Sulfate in FGF1/FGFR1 Signaling Complex”, Zhengliang L. Wu, Lijuan Zhang, Tomio Yabe, B. Kuberan, D. L. Beeler, A. Love, R. D. Rosenberg, Journal of Biological Chemistry, 278 (19), 17121-17129, 2003

“Analysis of Heparan Sulfate Oligosaccharides with Ion Pair-Reverse Phase Capillary High Performance Liquid Chromatography-Micro Electrospray Ionization Time-of-Flight Mass Spectrometry”, B. Kuberan, M. Lech, L. Zhang, Z. L. Wu, D. L. Beeler, R. D. Rosenberg, Journal of the American Chemical Society, 124 (29), 8707-8718, 2002

“A Method for Obtaining Equilibrium Tautomeric Mixtures of Reducing Sugars via Glycosylamines Using Non-Aqueous Media”, S. S. Allavudeen, B. Kuberan, D. Loganathan, Carbohydrate Research, 337 (10), 965-968, 2002

“A New Strategy for Defining Critical Functional Groups on Heparan Sulfate”, Zhengliang L Wu, Lijuan Zhang, David L. Beeler, B. Kuberan, Robert D. Rosenberg, FASEB Journal, 16 (6), 539-545, 2002

“Esterase Mediated Regioselective Deacetylation of Ulosonic Acid”, B. Kuberan, Q. Wang, M. Koketsu, R. J. Linhardt, Synthetic Communications, 32 (9), 1421-1426, 2002

“Chemoenzymatic Synthesis of Dermatan Sulfate Oligosaccharides as Arylsulfatase B and ±-L-Iduronidase Substrates”, F. Dasgupta, R. I. Masada, C. M. Starr, B. Kuberan, H. O. Yang, R. J. Linhardt, Glycoconjugate Journal, 17 (12), 829-834, 2000

“Stereoselective Synthesis of the ±-glycoside of a KDO “C”-Disaccharide”, M. Koketsu, B. Kuberan, R. J. Linhardt, Organic Letters, 2 (21), 3361-3363, 2000

“Preparation and Structural Determination of Dermatan Sulfate Derived Oligosaccharides”, H. O. Yang, N. S. Gunay, T. Toida, B. Kuberan, G. Yu, Y. S. Kim, R. J. Linhardt, Glycobiology, 10 (10), 1033-1040, 2000

“Carbohydrate Based Vaccines”, B. Kuberan, R. J. Linhardt, Current Organic Chemistry, 4 (6), 653-677, 2000 (review)

“Preparation and Isolation of Neoglycoconjugates Using Biotin-Streptavidin Complexes”, B. Kuberan, N. S. Gunay, J. S. Dordick, R. J. Linhardt, Glycoconjugate Journal, 16 (6), 271-281, 1999

“Isolation and Characterization of ≤-Cyclodextrin Sulfates by Preparative Gradient Polyacrylamide Gel Electrophoresis, Capillary Electrophoresis and Electrospray Ionization Mass Spectrometry”, R. E. Hileman, M. M. Siegel, K. Tabei, K. Balagurunathan, R. J. Linhardt, Electrophoresis, 19 (15), 2677 - 2681, 1998


BOOK CHAPTERS

"New Approaches to Study Structures of Heparan Sulfate Polysaccharides", Balagurunathan Kuberan, Miroslaw Lech, Robert D. Rosenberg, in Polysaccharides: Structural Diversity and Functional Versatility, 2nd Edition, S. Dumitriu, Ed., Marcel Dekker, New York, 2004
"Mechanism of Heparan Sulfate Biosynthesis"  Balagurunathan Kuberan, Robert D. Rosenberg, in Polysaccharides: Structural Diversity and Functional Versatility, 2nd Edition, S. Dumitriu, Ed., Marcel Dekker, New York, 2004


PATENTS

“Synthesis of Novel Xylosides and their potential uses thereof”, B. Kuberan, M. Ethirajan, X. Victor, V. Tran, K. Nguyen, U.S. Patent Pending, 2007

“Rapid Two Step Synthesis of Anticoagulants”, B. Kuberan, R. D. Rosenberg, U.S. Patent Pending, 2004

“Methods for Synthesizing Polysaccharides”, B. Kuberan, R. D. Rosenberg, US Patent Pending, 2004

“Methods for Synthesis of Sulfated Saccharides” B. Kuberan, R. D. Rosenberg, U.S. Patent # US 7, 655, 445 B2, 2010

“A Method for Obtaining Equilibrated Anomeric Mixture of Sugars Using Non-Aqueous Media”, D. Loganathan, S. S. Allavudeen, B. Kuberan, Indian Patent # 2430 / MAS / 98

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