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Kuberan Balagurunathan and Lab

Professor of Medicinal Chemistry

 

CONTACT

Phone: 801.587.9474

Fax: 801.585.6208

Email: kuby.balagurunathan@utah.edu

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.

Lab Information

Research Group Members

Kuberan Balagurunathan, Ph.D.

Principal Investigator

Current Students and Postdocs

Vimal Swarup

Bioengineering Graduate Student

(2009-Present)

Caitlin Paige Mencio

Neuroscience Graduate Student

(2009-Present)

Karthik Raman

Bioengineering Graduate Student

(2008-Present)

Thao Kim Nu Nguyen

Bioengineering Graduate Student

(2006-Present)

Vy My Tran

Bioengineering Graduate Student

(2006-Present)

Opportunities

Please email Dr. Kuberan Balagurunathan for inquiries or information. 

Publications

    PUBLICATIONS

    1. “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
    2. “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
    3. ” 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
    4. “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
    5. “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
    6. “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
    7. “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]
    8. “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
    9. “Click-Xylosides Mitigate Glioma Invasion In vitro”, Karthik Raman and B. Kuberan, Molecular BioSystems, 6, 1800-1802, 2010
    10. “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
    11. “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
    12. “RGD-Xyloside Conjugates Prime Glycosminoglycans”, Vy M. Tran, Xylophone V. Victor, James Yockman, B. Kuberan, Glycoconjugate Journal, 6, 625-633, 2010
    13. “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
    14. “Chemical Tumor Biology of Heparan Sulfate Proteoglycans”, Current Chemical Biology, Karthik Raman, B. Kuberan, Current Chemical Biology, 4, 20-31, 2010
    15. “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
    16. “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
    17. “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]
    18. “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
    19. “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
    20. “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
    21. “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
    22. “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
    23. “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
    24. “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
    25. “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
    26. “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
    27. “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
    28. “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
    29. “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
    30. “Esterase Mediated Regioselective Deacetylation of Ulosonic Acid”, B. Kuberan, Q. Wang, M. Koketsu, R. J. Linhardt, Synthetic Communications, 32 (9), 1421-1426, 2002
    31. “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
    32. “Stereoselective Synthesis of the ±-glycoside of a KDO “C”-Disaccharide”, M. Koketsu, B. Kuberan, R. J. Linhardt, Organic Letters, 2 (21), 3361-3363, 2000
    33. “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
    34. “Carbohydrate Based Vaccines”, B. Kuberan, R. J. Linhardt, Current Organic Chemistry, 4 (6), 653-677, 2000 (review)
    35. “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
    36. “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

    1. "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
    2. "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

    1. “Synthesis of Novel Xylosides and their potential uses thereof”, B. Kuberan, M. Ethirajan, X. Victor, V. Tran, K. Nguyen, U.S. Patent Pending, 2007
    2. “Rapid Two Step Synthesis of Anticoagulants”, B. Kuberan, R. D. Rosenberg, U.S. Patent Pending, 2004
    3. “Methods for Synthesizing Polysaccharides”, B. Kuberan, R. D. Rosenberg, US Patent Pending, 2004
    4. “Methods for Synthesis of Sulfated Saccharides” B. Kuberan, R. D. Rosenberg, U.S. Patent # US 7, 655, 445 B2, 2010
    5. “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