Disease-related Protein Glycoforms
 
Eric Dodds

Assistant Professor
Department of Chemistry
University of Nebraska-Lincoln
711 Hamilton Hall
Lincoln, NE 68588-0304
(402) 472-3592
edodds2@unl.edu

Education

Postdoctoral, Chemistry - University of Arizona
Ph.D., Chemistry - University of California, Davis
B.S., Biological Sciences, Chemistry - University of Alaska Anchorage

Research Overview

Research activities in the Dodds laboratory are concentrated on the conception and implementation of mass spectrometry based strategies for the analysis of biomolecules. More specifically, the group is focused on the development of new capabilities for carbohydrate and glycoconjugate analysis, with particular emphasis on site-specific determination of protein glycosylation and the distinction of carbohydrate isomers.

Additional areas of study include the structural interrogation of noncovalent biomolecular assemblies and the development of novel approaches for metabolomic analysis. In each of these areas, the Dodds group applies leading-edge tools and expertise in mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry to address longstanding bioanalytical challenges.

As part of the CIBC, the Dodds laboratory is working to establish a chemical understanding of the energy-dependent dissociation pathways of N-glycopeptides in tandem mass spectrometry (MS/MS), and to apply this understanding to delineate disease-associated alterations in the site-specific glycosylation of human alpha1-acid glycoprotein (AGP). Although the biomedical significance of disease-induced aberrations in protein glycosylation has been recognized for some time, significant challenges remain in translating these observations into robust disease biomarkers, and in establishing a detailed molecular understanding of how altered protein glycosylation affects various biomolecular interactions and signaling pathways. As our understanding of these processes continues to evolve, elucidation of site-specific glycosylation patterns will become increasingly important in the study of biomolecular interactions and signaling. A central tool for site-specific glycosylation analysis is the application of MS/MS to glycopeptides produced by proteolytic digestion of glycoproteins.

Dodds Figure

A highly desirable outcome of such analyses is to obtain information on both glycan topology and polypeptide sequence; however, this level of detail is not readily achieved by any single MS/MS method. To overcome this limitation, the Dodds group will address the following central hypothesis: for protonated N-glycopeptides, the vibrational energy required to selectively cleave the glycan or polypeptide is dictated by physicochemical characteristics of the glycopeptide; knowledge of these characteristics can be used to guide MS/MS experiments to obtain maximum structural information. As shown in the accompanying Figure, energy-resolved collision-induced dissociation (CID) spectra will be collected for a variety of glycopeptides with known structures, as well as unknown glycopeptides from complex glycoproteomic samples. The data will be mined to determine relationships between physicochemical properties and energy-resolved CID behavior. This information will then be used to enable a detailed site-specific characterization of disease-related human AGP glycoforms.

Selected Publications
  1. Discrimination of isomeric carbohydrates as the electron transfer products of group II cation adducts by ion mobility spectrometry and tandem mass spectrometry
    Y. Huang and E. D. Dodds
    Analytical Chemistry 87: 5664-5668 (2015)
  2. A comparison of energy-resolved vibrational activation / dissociation characteristics of protonated and sodiated high mannose N-glycopeptides
    F. Aboufazeli, V. Kolli, and E. D. Dodds
    Journal of the American Society for Mass Spectrometry, 26: 587-595 (2015)
  3. Combining DI-ESI-MS and NMR datasets for metabolic profiling
    D. D. Marshall, S. Lei, B. Worley, Y. Huang, A. Garcia-Garcia, R. Franco, E. D. Dodds, and R. Powers
    Metabolomics 11: 391-402 (2015)
  4. Engaging challenges in glycoproteomics: recent advances in MS-based glycopeptide analysis
    V. Kolli, K. N. Schumacher, and E. D. Dodds
    Bioanalysis 7: 113-131 (2015)
  5. A study of calibrant selection in measurement of carbohydrate and peptide ion-neutral collision cross sections by traveling wave ion mobility spectrometry
    A. S. Gelb, R. E. Jarratt, Y. Huang, and E. D. Dodds
    Analytical Chemistry 86: 11396-11402 (2014)
  6. Alterations in energy / redox metabolism induced by mitochondrial and environmental toxins: a specific role for glucose-6-phosphate-dehydrogenase and the pentose phosphate pathway in paraquat toxicity
    S. Lei, L. Zavala-Flores, A. Garcia-Garcia, R. Nandakumar, Y. Huang, N. Madayiputhiya, R. C. Stanton, E. D. Dodds, R. Powers, and R. Franco
    ACS Chemical Biology 9: 2032-2048 (2014)
  7. Collision-induced release, ion mobility separation, and amino acid sequence analysis of subunits from mass-selected noncovalent protein complexes
    D. Rathore and E. D. Dodds
    Journal of the American Society for Mass Spectrometry 25: 1600-1609 (2014)
  8. Energy-resolved collision-induced dissociation pathways of model N-linked glycopeptides: implications for capturing glycan connectivity and peptide sequence in a single experiment
    V. Kolli and E. D. Dodds
    Analyst 139: 2144-2153 (2014)