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Department of Chemistry and Chemical Biology at Rensselaer Chemistry and Chemical Biology
Robert J. Linhardt
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Robert J. Linhardt

Ann and John H. Broadbent, Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering
Professor, Department of Chemistry and Chemical Biology
Professor, Department of Biology
Professor, Department of Chemical and Biological Engineering
Professor, Department of Biomedical Engineering
Rensselaer Polytechnic Institute


Ph.D., Organic Chemistry, The Johns Hopkins University, 1979
M.A., Organic Chemistry, The Johns Hopkins University, 1977
B.S., Chemistry, Marquette University, 1975

Career Highlights:

After 21 years on the faculty of the University of Iowa, Linhardt joined Rensselaer in 2003 as a senior constellation professor. During his career in Iowa, he spent eight years as the university’s F. Wendell Miller Distinguished Professor of Chemistry and ten years as a member of the Executive Committee of the Center for Biocatalysis and Bioprocessing. Linhardt began his professional career with a three-year postdoctorate in chemical engineering at Massachusetts Institute of Technology.

Government agencies and numerous foundations and corporations have provided extensive funding for Linhardt’s research. An active contributor to professional publications, Linhardt has served on the editorial board of such top journals as the Journal of Biological Chemistry, Applied Biochemistry and Biotechnology, and the Journal of Carbohydrate Chemistry. He has published more than 525 research papers and holds 40 patents.

Among the many honors Linhardt has received include the Melville L. Wolfrom Award Award from the American Chemical Society (2010), Election to the rank of American Association for the Advancement of Science (AAAS) Fellow (2010), USP Award for an Innovative Response to a Public Health Challenge (2010), Scientific American 10 (2009), Claude S. Hudson Award from the American Chemical Society (2003), the Volweiler Research Achievement Award in Pharmaceutical Sciences (1999), the Horace S. Isbell Award from The Carbohydrate Division of the American Chemical Society (1994), the Iowa Regents Award for Faculty Excellence (1992), and the University of Iowa Excellence in Teaching Award (1989). 

Linhardt is a member of many professional societies including American Chemical Society, American Society of Biochemistry and Molecular Biology, American Association for the Advancement of Science (AAAS), Society for Glycobiology, American Association of Colleges of Pharmacy, and American Association of Pharmaceutical Scientists. Linhardt has been a consultant to industry and government for nearly 30 years.

Research Areas:

Linhardt is internationally known for his research on the study of bioactive carbohydrates, particularly the complex polysaccharide heparin. Heparin is a major clinical anticoagulant with more than 500 million doses used worldwide each year. Heparin and related molecules exhibit a large number of newly discovered biological activities and have great therapeutic potential.

Research in his laboratory focuses on complex carbohydrates. Proteoglycans and other glycoconjugates are prepared by fermentation using recombinant technology, extraction from tissues, or by chemical and enzymatic synthesis. After determining the structure of these molecules, his group studies their biological activities. By establishing a structure-activity relationship, these molecules often become lead compounds for new drug development.

Mapping of the human glycome is underway with a focus on heparan sulfate proteoglycans. An artificial Golgi is being developed based on a digital microfluidics platform to study glycan biosynthesis. Carbohydrate structures are being determined, and biochips and microarrays are being used as tools for glycomic screening.

Linhardt also is conducting biochemistry and structural biology studies which focus on the preparation, purification, and characterization of carbohydrates and glycoconjugates. His group develops methods to purify these glycoconjugates and determine their structure by microsequencing using mass spectrometry (MS).

Biophysical chemists in his laboratory study the kinetics and thermodynamics of protein-carbohydrate interactions, relying primarily on isothermal titration calorimetry and surface plasmon resonance (SPR) spectrometry. X-ray crystallography and nuclear magnetic resonance (NMR) solution structure analysis are used in conjunction with molecular modeling to determine the molecular contacts in the protein carbohydrate complex.

The Linhardt group also studies the medical application of nanomaterials.  This research specifically focuses on carbohydrate-containing nanocomposites in medical and power storage devices.  These implantable devices may someday be used in biosensor, therapeutic and nanorobotic applications.   

Linhardt’s synthetic chemistry group relies on chemical and enzymatic synthesis to prepare target carbohydrates for biological evaluation. The group’s current focus is to prepare acidic carbohydrates. Targets include: sialic acid C-glycoside analogues as vaccines and therapeutics as well as the chemoenzymatic synthesis of heparin and heparin oligosaccharides for therapeutic evaluation.

Selected Publications:

Chen W, Li L, Du Z, Liu J, Reitter JN, Mills KV, Linhardt RJ, Wang C. "Intramolecular disulfide bond between catalytic cysteines in an intein precursor" J. Am. Chem. Soc. 2012, in press.

Yang B.; Chang Y.; Weyers A. M.; Sterner E.; Linhardt R. J., "Disaccharide analysis of glycosaminoglycan mixtures by ultra-performance liquid chromatography-mass spectrometry" J. Chromatogr. A, 2012, 1225, 91–98.

Masuko S, Bera S, Green DE, Weïwer M, Liu J, Deangelis PL, Linhardt RJ. "Chemoenzymatic synthesis of uridine diphosphate-GlcNAc and uridine diphosphate-GalNAc analogs for the preparation of unnatural glycosaminoglycans" J. Org. Chem. 2012, 77, 1449-56

Ly M.; Leach III F. E.; Laremore T. N.; Toida T.; Amster I. J.; Linhardt R.J. "The proteoglycan bikunin has a defined sequence" Nature Chemical Biology, 2011, 7, 827-833.

Miao J.; Miyauchi M.; Dordick J. S.; Linhardt R. J. "Preparation and characterization of electrospun core sheath nanofibers from multiwall carbon nanotubes and poly (vinyl pyrrolidone)" J. Nanosci. Nanotechnol. 2011, 1-17.

Xu Y.; Masuko S.; Takieddin M.; Xu H.; Liu R.; Jing J.; Mousa S.; Linhardt R. J.; Liu J. "Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins" Science, 2011, 334, 498-501.

Zhao, W.; Garron, M.-L.; Yang, B.; Xiao, Z.; Esko, J. D.; Cygler, M.; Linhardt, R. J. "Asparagine 405 of Heparin Lyase Ii Prevents the Cleavage of Glycosidic Linkages Proximate to a 3-O-Sulfoglucosamine Residue" FEBS Lett. 2011, 585, 2461-2466.

Yang, B.; Weyers, A.; Baik, J. Y.; Sterner, E.; Sharfstein, S.; Mousa, S. A.; Zhang, F.; Dordick, J. S.; Linhardt, R. J. "Ultra-Performance Ion-Pairing Liquid Chromatography with on-Line Electrospray Ion Trap Mass Spectrometry for Heparin Disaccharide Analysis" Anal. Biochem. 2011, 415, 59-66.

Yang, B.; Solakyildirim, K.; Chang, Y.; Linhardt, R. J. "Hyphenated Techniques for the Analysis of Heparin and Heparan Sulfate" Anal. Bioanal.Chem. 2011, 399, 541-557.

Xiao, Z.; Zhao, W.; Yang, B.; Zhang, Z.; Guan, H.; Linhardt, R. J. "Heparinase 1 Selectivity for the 3,6-Di-O-Sulfo-2-Deoxy-2-Sulfamido-Alpha-D-Glucopyranose (1,4) 2-O-Sulfo-Alpha-L-Idopyranosyluronic Acid (Glcns3s6s-Idoa2s) Linkages" Glycobiology 2011, 21, 13-22.

Xiao, Z.; Tappen, B. R.; Ly, M.; Zhao, W.; Canova, L. P.; Guan, H.; Linhardt, R. J. "Heparin Mapping Using Heparin Lyases and the Generation of a Novel Low Molecular Weight Heparin" J. Med. Chem. 2011, 54, 603-610.

Wang, Z.; Yang, B.; Zhang, Z.; Ly, M.; Takieddin, M.; Mousa, S.; Liu, J.; Dordick, J. S.; Linhardt, R. J. "Control of the Heparosan N-Deacetylation Leads to an Improved Bioengineered Heparin" Appl. Microbiol. Biotechnol. 2011, 91, 91-99.

Wang, Z.; Flax, L. A.; Kemp, M. M.; Linhardt, R. J.; Baron, M. J. "Host and Pathogen Glycosaminoglycan-Binding Proteins Modulate Antimicrobial Peptide Responses in Drosophila Melanogaster" Infection and Immunity 2011, 79, 606-616.

Vongchan, P.; Wutti-In, Y.; Sajomsang, W.; Gonil, P.; Kothan, S.; Linhardt, R. J. "N,N,N-Trimethyl Chitosan Nanoparticles for the Delivery of Monoclonal Antibodies against Hepatocellular Carcinoma Cells" Carbohydr. Polym. 2011, 85, 215-220.

Park, Y.; Hong, Y. N.; Weyers, A.; Kim, Y. S.; Linhardt, R. J. "Polysaccharides and Phytochemicals: A Natural Reservoir for the Green Synthesis of Gold and Silver Nanoparticles" IET Nanobiotechnol. 2011, 5, 69-78.

Otto, N. J.; Solakyildirim, K.; Linhardt, R. J.; DeAngelis, P. L. "Comamonas Testosteronan Synthase, a Bifunctional Glycosyltransferase That Produces a Unique Heparosan Polysaccharide Analog" Glycobiology 2011, 21, 1331-1340.

Mora-Pale, M.; Meli, L.; Doherty, T. V.; Linhardt, R. J.; Dordick, J. S. "Room Temperature Ionic Liquids as Emerging Solvents for the Pretreatment of Lignocellulosic Biomass" Biotechnol. Bioeng. 2011, 108, 1229-1245.

Miyauchi, M.; Simmons, T. J.; Miao, J.; Gagner, J. E.; Shriver, Z. H.; Aich, U.; Dordick, J. S.; Linhardt, R. J. "Electrospun Polyvinylpyrrolidone Fibers with High Concentrations of Ferromagnetic and Superparamagnetic Nanoparticles" ACS Appl. Mater. Interfaces 2011, 3, 1958-1964.

Ly, M.; Wang, Z.; Laremore, T. N.; Zhang, F.; Zhong, W.; Pu, D.; Zagorevski, D. V.; Dordick, J. S.; Linhardt, R. J. "Analysis of E. Coli K5 Capsular Polysaccharide Heparosan" Anal. Bioanal.Chem. 2011, 399, 737-745.

Liu, Z.; Xiao, Z.; Masuko, S.; Zhao, W.; Sterner, E.; Bansal, V.; Fareed, J.; Dordick, J.; Zhang, F.; Linhardt, R. J. "Mass Balance Analysis of Contaminated Heparin Product" Anal. Biochem. 2011, 408, 147-156.

Leach, F. E., III; Wolff, J. J.; Xiao, Z.; Ly, M.; Laremore, T. N.; Arungundram, S.; Al-Mafraji, K.; Venot, A.; Boons, G.-J.; Linhardt, R. J.; Amster, I. J. "Negative Electron Transfer Dissociation Fourier Transform Mass Spectrometry of Glycosaminoglycan Carbohydrates" Eur. J. Mass Spectrom. 2011, 17, 167-176.

Khurana, A.; Liu, P.; Mellone, P.; Lorenzon, L.; Vincenzi, B.; Datta, K.; Yang, B.; Linhardt, R. J.; Lingle, W.; Chien, J.; Baldi, A.; Shridhar, V. "Hsulf-1 Modulates Fgf2-and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells" Cancer Research 2011, 71, 2152-2161.

Garg, H. G.; Mrabat, H.; Yu, L.; Hales, C. A.; Li, B.; Moore, C. N.; Zhang, F.; Linhardt, R. J. "Anti-Proliferative Effects of O-Acyl-Low-Molecular-Weight Heparin Derivatives on Bovine Pulmonary Artery Smooth Muscle Cells" Glycoconjugate J. 2011, 28, 419-426.

Bera, S.; Linhardt, R. J. "Design and Synthesis of Unnatural Heparosan and Chondroitin Building Blocks" J. Org. Chem. 2011, 76, 3181-3193.

Beaudet, J. M.; Weyers, A.; Solakyildirim, K.; Yang, B.; Takieddin, M.; Mousa, S.; Zhang, F.; Linhardt, R. J. "Impact of Autoclave Sterilization on the Activity and Structure of Formulated Heparin" J. Pharm. Sci. 2011, 100, 3396-3404.

Anand, G.; Zhang, F.; Linhardt, R. J.; Belfort, G. "Protein-Associated Water and Secondary Structure Effect Removal of Blood Proteins from Metallic Substrates" Langmuir 2011, 27, 1830-1836.

Wang, Z.; Ly, M.; Zhang, F.; Zhong, W.; Suen, A.; Hickey, A. M.; Dordick, J. S.; Linhardt, R. J. "E. Coli K5 Fermentation and the Preparation of Heparosan, a Bioengineered Heparin Precursor" Biotechnol. Bioeng. 2010, 107, 964-973.

Liu, Z.; Masuko, S.; Solakyildirim, K.; Pu, D.; Linhardt, R. J.; Zhang, F. "Glycosaminoglycans of the Porcine Central Nervous System" Biochemistry 2010, 49, 9839-9847.

Liu, R.; Xu, Y.; Chen, M.; Weiwer, M.; Zhou, X.; Bridges, A. S.; DeAngelis, P. L.; Zhang, Q.; Linhardt, R. J.; Liu, J. "Chemoenzymatic Design of Heparan Sulfate Oligosaccharides" J. Biol. Chem. 2010, 285, 34240-34249.

Laremore, T. N.; Ly, M.; Zhang, Z.; Solakyildirim, K.; McCallum, S. A.; Owens, R. T.; Linhardt, R. J. "Domain Structure Elucidation of Human Decorin Glycosaminoglycans" Biochem. J 2010, 431, 199-205.

Beccati, D.; Roy, S.; Yu, F.; Gunay, N. S.; Capila, I.; Lech, M.; Linhardt, R. J.; Venkataraman, G. "Identification of a Novel Structure in Heparin Generated by Potassium Permanganate Oxidation" Carbohydr. Polym. 2010, 82, 699-705.

Liu, H.; Zhang, Z.; Linhardt, R. J. "Lessons Learned from the Contamination of Heparin" Nat. Prod. Rep. 2009, 26, 313-321.

Lee, S. H.; Doherty, T. V.; Linhardt, R. J.; Dordick, J. S. "Ionic Liquid-Mediated Selective Extraction of Lignin from Wood Leading to Enhanced Enzymatic Cellulose Hydrolysis" Biotechnol. Bioeng. 2009, 102, 1368-1376.

Guerrini, M.; Beccati, D.; Shriver, Z.; Naggi, A.; Viswanathan, K.; Bisio, A.; Capila, I.; Lansing, J. C.; Guglieri, S.; Fraser, B.; Al-Hakim, A.; Gunay, N. S.; Zhang, Z.; Robinson, L.; Buhse, L.; Nasr, M.; Woodcock, J.; Langer, R.; Venkataraman, G.; Linhardt, R. J.; Casu, B.; Torri, G.; Sasisekharan, R. "Oversulfated Chondroitin Sulfate Is a Contaminant in Heparin Associated with Adverse Clinical Events" Nature Biotechnology 2008, 26, 669-675.

Wolff, J. J.; Chi, L.; Linhardt, R. J.; Amster, I. J. "Distinguishing Glucuronic from Iduronic Acid in Glycosaminoglycan Tetrasaccharides by Using Electron Detachment Dissociation" Anal. Chem. 2007, 79, 2015-2022.

Wolff, J. J.; Amster, I. J.; Chi, L.; Linhardt, R. J. "Electron Detachment Dissociation of Glycosaminoglycan Tetrasaccharides" J. Am. Soc. Mass. Spectrom. 2007, 18, 234-244.

Pushparaj, V. L.; Shaijumon, M. M.; Kumar, A.; Murugesan, S.; Ci, L.; Vajtai, R.; Linhardt, R. J.; Nalamasu, O.; Ajayan, P. M. "Flexible Energy Storage Devices Based on Nanocomposite Paper" PNAS 2007, 104, 13574-13577.

Laremore, T. N.; Zhang, F.; Linhardt, R. J. "Ionic Liquid Matrix for Direct Uv-Maldi-Tof-Ms Analysis of Dermatan Sulfate and Chondroitin Sulfate Oligosaccharides" Anal. Chem. 2007, 79, 1604-1610.

Goetz, R.; Beenken, A.; Ibrahimi, O. A.; Kalinina, J.; Olsen, S. K.; Eliseenkova, A. V.; Xu, C.; Neubert, T. A.; Zhang, F.; Linhardt, R. J.; Yu, X.; White, K. E.; Inagaki, T.; Kliewer, S. A.; Yamamoto, M.; Kurosu, H.; Ogawa, Y.; Kuro-o, M.; Lanske, B.; Razzaque, M. S.; Mohammadi, M. "Molecular Insights into the Klotho-Dependent, Endocrine Mode of Action of Fibroblast Growth Factor 19 Subfamily Members" Mol. Cell. Biol. 2007, 27, 3417-3428.


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