Vernon Reinhold, Ph.D.

Vernon Reinhold, Ph.D.

Research Professor

Educational Background:

Ph.D., University of Vermont, 1965.

Research:

Glycosylation is one of the most frequent post-translational modifications. Interest in the biological roles of lipid and protein glycosylation has intensified because of increasing examples of their importance as recognition determinants. It has been estimated that about 0.5-1.0% of the translated mammalian genome participates in oligosaccharide production and function and many specific roles have now been documented to involve glycan structures. Four areas of research that have received considerable attention are (i) development and differentiation, (ii) cell adhesion and inflammation, (iii) cancer and metastasis, and (iv) host-pathogen interactions in infection diseases.

The biosynthesis of glycans is catalyzed by glycosyltransferases, a family of 100 or more enzymes which transfer a sugar residue from a nucleotide-sugar donor to an acceptor which can be a sugar, an amino acid, or a lipid. These glycosyltransferases are classified on the basis of the carbohydrate residue they transfer, (e.g., galactosyltransferases, sialyltransferases, fucosyltransferases), and are distinguished by the sugar they recognize as an acceptor. Two fundamental features make structural characterization of these materials extremely difficult: product structures are frequently branched with considerable isomerism, and individual moieties are controlled at the level of transferase expression (not a direct product to be identified from the genome).

Work in our laboratory has focused strongly on methods development in past years and more recently on application of these strategies and techniques to relate carbohydrate detailed structure to function. For reasons of sensitivity and specificity these methods depend heavily on mass spectrometry and their adjunct techniques. Latest studies have involved the use of ion trapping to determine carbohydrate structures where specific ions are selected for activation, collision, and measurement multiple times, MSn. This ability to isolate substructures for further characterization has become of vital importance to understand the detailed linkage and branching patterns inherent in lipid and protein glycosylation.

Publications:

Ashline, D. J.; Hanneman, A. J.; Zhang, H.; Reinhold, V. N., Structural Documentation of Glycan Epitopes: Sequential Mass Spectrometry and Spectral Matching. J Am Soc Mass Spectrom. 2014 Jan 3. [Epub ahead of print]

Reinhold, V.; Zhang, H.; Hanneman, A.; Ashline, D., Toward a platform for comprehensive glycan sequencing. Mol Cell Proteomics 2013, 12 (4), 866-73.

Zhou, H.; Hanneman, A. J.; Chasteen, N. D.; Reinhold, V. N., Anomalous N-glycan structures with an internal fucose branched to GlcA and GlcN residues isolated from a mollusk shell-forming fluid. J Proteome Res 2013, 12 (10), 4547-55.

Jiao, J.; Zhang, H.; Reinhold, V. N., High Performance IT-MS Sequencing of Glycans (Spatial Resolution of Ovalbumin Isomers). Int J Mass Spectrom 2011, 303 (2-3), 109-117.

Prien, J. M.; Ashline, D. J.; Lapadula, A. J.; Zhang, H.; Reinhold, V. N., The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap MS. J Am Soc Mass Spectrom 2009, 20 (4), 539-56.

Prien, J. M.; Huysentruyt, L. C.; Ashline, D. J.; Lapadula, A. J.; Seyfried, T. N.; Reinhold, V. N., Differentiating N-linked glycan structural isomers in metastatic and nonmetastatic tumor cells using sequential mass spectrometry. Glycobiology 2008, 18 (5), 353-66.

Anthony, R. M.; Nimmerjahn, F.; Ashline, D. J.; Reinhold, V. N.; Paulson, J. C.; Ravetch, J. V., Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 2008, 320 (5874), 373-6.

Lau, K. S.; Partridge, E. A.; Grigorian, A.; Silvescu, C. I.; Reinhold, V. N.; Demetriou, M.; Dennis, J. W., Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 2007, 129 (1), 123-34.

Ashline, D. J.; Lapadula, A. J.; Liu, Y. H.; Lin, M.; Grace, M.; Pramanik, B.; Reinhold, V. N., Carbohydrate structural isomers analyzed by sequential mass spectrometry. Anal Chem 2007, 79 (10), 3830-42.

Lapadula, A. J.; Hatcher, P. J.; Hanneman, A. J.; Ashline, D. J.; Zhang, H.; Reinhold, V. N., Congruent strategies for carbohydrate sequencing. 3. OSCAR: an algorithm for assigning oligosaccharide topology from MSn data. Anal Chem 2005, 77 (19), 6271-9.

Zhang, H.; Singh, S.; Reinhold, V. N., Congruent strategies for carbohydrate sequencing. 2. FragLib: an MSn spectral library. Anal Chem 2005, 77 (19), 6263-70.

Ashline, D.; Singh, S.; Hanneman, A.; Reinhold, V., Congruent strategies for carbohydrate sequencing. 1. Mining structural details by MSn. Anal Chem 2005, 77 (19), 6250-62.

Vernon Reinhold
Gregg Hall, Room 440
Durham, NH 0
Phone: 
(603) 862-2527