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Guest Bio: Robert J. Linhardt, PhD

After 21 years on the faculty of the University of Iowa (UI), Robert J. Linhardt, PhD, joined Rensselaer in 2003 as a senior Constellation Professor. During his career in Iowa, he spent eight years as the UI 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 three-years of postdoctoral study in Chemical Engineering at MIT. Government agencies and numerous foundations and corporations have provided extensive funding for Linhardt’s research. He has published more than 950 research papers and holds 50 patents.

Among the many honors Linhardt has received include: recipient of the Karl Meyer Award in Glycobology (2019); a Fellow National Academy of Inventors (NAI) (2015); recipient of the Melville L. Wolfrom Award from the American Chemical Society (2010), a Fellow of the American Association for the Advancement of Science (AAAS) (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), Volwiler Research Achievement Award in Pharmaceutical Sciences (1999), Horace S. Isbell Award from the Carbohydrate Division of the American Chemical Society (1994), the Iowa Regents Award for Faculty Excellence (1992), and the UI Excellence in Teaching Award (1989).

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 analogues as diagnostics and therapeutics as well as the chemoenzymatic synthesis of heparin and heparin oligosaccharides for therapeutic evaluation. Recent efforts include the application of metabolic engineering to prepare glycans Linhardt was recently appointed as the Co-Director of Rensselaer’s Heparin Applied Research Center (HARC) that is working towards the goal of commercialization of a safe bioengineered heparin.