School of Engineering

Robert J. Linhardt
Professor
Acting Director of Center for Biotechnology and Interdisciplinary Studies http://www-heparin.rpi.edu/

Department Affiliation:

Rensselaer Polytechnic Institute
Department of Chemical and Biological Engineering

Education:

Ph.D., The Johns Hopkins University, Baltimore, MD
Organic Chemistry

M.S., The Johns Hopkins University, Baltimore, MD
Organic Chemistry

B.S., Marquette University, Milwaukee, WI
Chemistry

Background:

Professor Linhardt received his B.S. in Chemistry in 1975 from Marquette University and his M.A. and Ph.D. in Organic Chemistry from Johns Hopkins University in 1977, 1979. He was a postdoctoral fellow from 1979-1982, in Chemical Engineering at Massachusetts Institute of Technology. He joined the faculty of the University of Iowa in 1982 rising through the ranks to become the F. Wendell Miller Distinguished Professor of Chemistry, Medicinal and Natural Products Chemistry and Chemical and Biochemical Engineering prior to joining the faculty of Rensselaer in 2003. He has received the 1992 Iowa Regents Award for Faculty Excellence, the 1994 Horace S. Isbell Award from the American Chemical Society, the 1999 Volwiler Research Achievement Award, and the 2003 Claude S. Hudson Award in Carbohydrate Chemistry from the American Chemical Society.

Read More: http://www-heparin.rpi.edu/

Research Interests:

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

Synthetic Carbohydrate Chemistry

Some carbohydrates are not accessible from natural sources. Our carbohydrate chemistry group relies on chemical and enzymatic synthesis to prepare target carbohydrates for biological evaluation. The current focus of this group is to prepare acidic carbohydrates, particularly ones that are catabolically stable. Several current targets include: chemoenzymatic synthesis of sulfated carbohydrates; sTn C-glycoside tumor antigen analog, for use as a cancer vaccine; GM3 and GM4 Cglycoside, gangliosides important in regeneration of damaged nerve fibers; and polysialic acid C-glycoside as a meningitis vaccine. Combinatorial solid phase synthesis of acidic carbohydrates for high through-put activity screening is being investigated to prepare carbohydrate-based anti-viral agents. New solvents, such as room temperature ionic liquids (RTILs) are also being investigated in chemoenzymatic synthesis of carbohydrates.

Glycobiology/Glycomics

With the sequencing of the human genome the attention of the research community has turned from genomics to proteomics, the study of the proteome. Our laboratory takes a long-term, postproteomic view in its study of the glycome. We are currently surveying the structure and function of acidic carbohydrates from various tissues of normal mice and knock-out mice (missing critical glycosyltransferases involved in glycan biosynthesis). The goal is to relate genotypes to observed phenotypes through glycan structure-function relationships.

Biochemistry and Structural Biochemistry

This project area focuses on the preparation, purification and characterization of carbohydrates and glycoconjugates. We have developed a variety of novel separation methods based on chromatography and electrophoresis. Structures are determined by microsequencing techniques first established in our laboratory and by NMR and MS analysis.

Biophysical Chemistry

Most carbohydrates exhibit biological activity by modulating the activity of proteins, such as enzymes and receptors. The biophysical chemistry subgroup studies the kinetics and thermodynamics of protein-carbohydrate interaction. We rely primarily on isothermal titration calorimetry to study interaction thermodynamics and surface plasmon resonance spectrometry to study interaction kinetics. Finally, x-ray crystallography and NMR solution structure is used in conjunction with molecular modeling to examine the molecular contacts in the protein carbohydrate complex.