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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:

Farrán, A; Cai, C; Sandoval, M; Xu, Y; Liu, J; Hernáiz, M J; Linhardt, R J Green solvents in carbohydrate chemistry: from raw materials to fine chemicals, Chem Rev, 2015, 115, 6811-6853.

Cress, B F; Toparlak, Ö D; Guleria, S; Lebovich, M; Stieglitz, J T; Englaender, J A; Jones, J A; Linhardt, R J; Koffas, M A G CRISPathBrick: Modular Combinatorial Assembly of Type II-A CRISPR Arrays for dCas9-Mediated Multiplex Transcriptional Repression in E coli, ACS Synth Biol, 2015, 4, 987–1000.

Schaub, N J; Le Beux, C; Miao, J; Linhardt, R J; Alauzun, J G; Laurencin, D; Gilbert, R J The effect of surface modification of aligned poly-L-lactic acid electrospun fibers on fiber degradation and neurite extension, PLoS One, 2015, 10, 0136780.

Sun, X; Li, L; Overdier, K H; Ammons, L A; Douglas, I S; Burlew, C C; Zhang, F; Schmidt, E P; Chi, L; Linhardt, R J Analysis of total human urinary glycosaminoglycan disaccharides by liquid chromatography-tandem mass spectrometry, Anal Chem, 2015, 87, 6220−6227.

Li, G; Tian, F; Zhang, L; Xue, C; Li, L; Linhardt, R J Glycosaminoglycanomics of cultured cells using a rapid and sensitive LC-MS/MS approach, ACS Chem Biol, 2015, 10, 1303-1310.

Higashi, K; Takeuchi, Y; Mukuno, A; Tomitori, H; Miya, M; Linhardt, R J; Toida, T Composition of glycosaminoglycans in elasmobranchs including several deep-sea sharks: Identification of chondroitin/dermatan sulfate from the dried fins of Isurus oxyrinchus and Prionace glauca, PLoS One, 2015, 0120860.

Dimitrievska, S; Cai, C; Weyers, A; Lin, T; Sundaram, S; Spiegel, D A; Kyriakides, T R; Miao, J; Li, G; Niklason, L; Linhardt, R J Click-coated, heparinized, decellularized vascular grafts, Acta Biomateriala, 2015, 13, 177–187.

He, W; Fu, L; Li, G; Jones, J A; Linhardt, R J; Koffas, M Production of chondroitin in metabolically engineered E coli, Metabol Eng, 2015, 27, 92-100.

Liu, J; Linhardt, RJ Chemoenzymatic synthesis of heparan sulfate and heparin, Nat Prod Rep, 2014, 31, 1676–1685.

Zheng, Y; Miao, J; Linhardt, R J; Simmons, T J Nanoparticle coating during wet electrospinning of cellulose, J Mat Chem A, 2014, 2, 15029–15034.

Cress, B F; Englaender, J A; He, W; Kasper, D; Linhardt, R J; Koffas, M A G Masquerading microbial pathogens: Capsular polysaccharides mimic the host-tissue molecules FEMS Microbiol Rev, 2014, 38, 660–697.

Li, G; Steppich, J; Wang, Z; Sun, Y; Xue, C; Linhardt, R J; Li, L Bottom-up LMWH analysis using LC-FTMS for extensive characterization, Anal Chem, 2014, 86, 6626−6632

Cai, C; Dickinson, D M; Li, L; Masuko, S; Suflita, M; Schultz, V; Bhaskar, U; Nelson, S D; Liu, J; Linhardt, R J Fluorous-assisted chemoenzymatic synthesis of heparan sulfate oligosaccharides, Org Lett, 2014, 16, 2240−2243. 

Sterner, E; Masuko, S; Li, G; Li, L; Green, D E; Otto, N J; Xu, Y; DeAngelis, P L; Liu, J; Dordick, J S; Linhardt, R J Fibroblast growth factor-based signaling through synthetic heparan sulfate block copolymers studied using high-cell density 3D cell printing, J Biol Chem, 2014, 289, 9754–9765.

Joo, E-J; Weyers, A; Li, G; Gasimli, L; Li, L; Choi, W J; Lee, K B; Linhardt, R J Carbohydrate-containing molecules as potential biomarkers in colon cancer, Omics, 2014, 18, 231-241.

Xu, Y; Cai, C; Chandarajoti, K; Hsieh, P –H; Li, L; Pham, T Q; Sparkenbaugh, E M; Sheng, J; Key, N S; Pawlinski, R; Harris, E N; Linhardt, R J; Liu J Homogeneous low molecular weight heparins with reversible anticoagulant activity, Nat Chem Biol, 2014, 10, 248-250. 

Zhang, B; Xiao, W; Qiu, H; Zhang, F; Moniz, H; Jaworski, A; Condac, E; Gutierrez-Sanchez, G; Heiss, C; Clugston, R; Azadi, P; Greer, J J; Bergmann, C; Moremen, K; Li, D Y; Linhardt, R J; Esko, J D; Wang, L Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia, J Clin Invest, 2014, 124, 209-221.

Kamhi, E; Joo, E J; Dordick, J S; Linhardt, R J Glycosaminoglycans in infectious disease, Biol Rev, 2013, 88, 928–943.

Chang, Y; Cai, C; Li, L; Miao, J; Ucaturk, E; Li, G; Ly, M; Linhardt, RJ Ultrasensitive detection and quantification of acidic disaccharides using capillary electrophoresis and quantum dot-based fluorescence resonance energy transfer, Anal Chem, 2013, 85, 9356−9362. 

Cai, C; Li, L; Harvey, C; Liu, J; Linhardt, RJ Toward the chemoenzymatic synthesis of heparan sulfate oligosaccharides: Oxidative cleavage of p-nitrophenyl group with ceric ammonium salts, Tet Lett, 2013, 54, 4471–4474.

Simmons, T J; Maeda, N; Dordick, J S; Linhardt, R J Self-assembly of carbon nanotube films from room temperature ionic liquids, Carbon, 2013, 58, 226–231.

Cai, C; Edgar, K; Liu, J; Linhardt, RJ Preparation and application of a clickable acceptor for enzymatic synthesis of heparin oligosaccharides, Carbohydr Res 2013, 372, 30–34.

Li, L; Zhang, F; Zaia, J; Linhardt, R J Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS, Anal Chem 2012, 84, 8822−8829.

Kwon, S-J; Lee, K-B; Solakyildirim, K; Masuko, S; Ly, M; Zhang, F; Li, L; Dordick, J S; Linhardt, R J Signal amplification by Glyco-qPCR for ultrasensitive detection of carbohydrates: Applications in glycobiology, Angew Chemie, 2012, 51, 11800 –11804.

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 RJ The proteoglycan bikunin has a defined sequence Nature Chemical Biology, 2011, 7, 827-833.

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.

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.

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.

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.

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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