Pomeroy Professor – Analytical Chemistry, Mass Spectrometry, Proteomics

Research and/or Creative Works

My research has used mass spectrometry along with stable isotopically labeled tracers and kinetic models to answer questions of human physiology and biochemistry. The research program of my group in chemistry focuses on developing new methods and techniques of mass spectrometry to measure the biological molecules and using stable isotopically labeled tracers, their rates of production and disposal.

Much of our research is focused upon amino acid and protein metabolism in humans. Students are encouraged as part of their thesis work to apply methods developed to clinical studies of metabolism in humans. Many simple metabolic questions have never been answered in humans. For example, we do not know which pathways regulate the metabolism of several important amino acids in humans.

Proteins have many functions from being the basic unit of our muscles to enzymes to being key signaling molecules. The regulation of all of this functions is complex and often involves posttranslational modification (PTM) of proteins through phosphorylation and other covalent changes.  An area of research has been development of proteomic methods for quantifying PTMs.

Mass spectrometry has been widely applied for compound identification, but precise measurement of isotopes in biological compounds has received less attention. Gas chromatography-mass spectrometry (GCMS), liquid chromatography-mass spectrometry (LCMS), and isotope ratio mass spectrometry (IRMS) instrumentation are all available and are used for research in our group to measure stable isotope ratio tracers in biological samples. LCMS has been particularly useful for developing methods in our group to quantify PTM of proteins for both phosphorylation and glycosylation.

The figure below from the M.J. Previs 2008 Anal. Chem. paper highlights the scheme we have developed to quantify phosphorylation of proteins at multiple sites using a tryptic digest of proteins and LCMS analysis. The key to the method is to perform the phosphorylation quantification without having to measure the phosphorylated peptide per se. This approach greatly simplifies the measurement scheme and does not require use of any isotopically labeled standards.

Publications

EJ Kasarskis, MS Mendiondo, DE Matthews, H Mitsumoto, R Tandan, Z Simmons, MB Bromberg & RJ Kryscio: Estimating daily energy expenditure in individuals with amyotrophic lateral sclerosis. Am. J. Clin. Nutr. 99: 792-803, 2014.

L Holm, B O'Rourke, D Ebenstein, MJ Toth, R Bechshoeft, NH Holstein-Rathlou, M Kjaer & DE Matthews: Determination of steady state protein breakdown rate in vivo by the disappearance of protein-bound tracer-labeled amino acids: a method applicable in humans. Am. J. Physiol. Endocrinol. Metab. 308: E895-E907, 2013.

J Krudysz-Amblo, ME Jennings, T Knight, DE Matthews, KG Mann & S Butenas: Disulfide reduction abolishes tissue factor cofactor function. Biochim. Biophys. Acta 1830: 3489-3496, 2013.

PC Spiess, B Deng, RJ Hondal, DE Matthews & A van der Vliet: Proteomic profiling of acrolein adducts in human lung epithelial cells. J. Proteomics 74: 2380-2394, 2011.

J Krudysz-Amblo, ME Jennings, DE Matthews, KG Mann & S Butenas: Differences in the fractional abundances of carbohydrates of natural and recombinant human tissue factor. Biochim. Biophys. Acta 1810: 398-405, 2011.

D Beauchemin & DE Matthews: Elemental and Isotope Ratio Mass Spectrometry. The Encyclopedia of Mass Spectrometry, vol 5, M. L. Gross & R. M. Caprioli, eds. Oxford, UK: Elsevier, 2010, 1-1088.

Y Lamers, B O'Rourke, LR Gilbert, C Keeling, DE Matthews, PW Stacpoole & JF Gregory, III: Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women. Am. J. Clin. Nutr. 90: 336-343, 2009.

MJ Previs, P VanBuren, KJ Begin, JO Vigoreaux, MM LeWinter & DE Matthews: Quantification of protein phosphorylation by liquid chromatography mass spectrometry. Anal. Chem. 80: 5864-5872, 2008.

SM McCarthy, PF Bove, DE Matthews, T Akaike & A van der Vliet: Nitric oxide regulation of MMP-9 activation and its relationship to modifications of the cysteine switch. Biochemistry 47: 5832-5840, 2008.

TM Thornton, G Pedraza-Alva, B Deng, CD Wood, A Aronshtam, JL Clements, G Sabio, RJ Davis, DE Matthews, B Doble & M Rincon: Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation. Science 320: 667-670, 2008.

Jennings, M.E., II & Matthews, D.E.: Determination of Complex Isotopomer Patterns in Isotopically Labeled Compounds by Mass Spectrometry, Anal. Chem. 2005, 77, 6435-44.

MacCoss, M.J. & Matthews, D.E.: Quantitative Mass Spectrometry for Proteomics: Teaching a New Dog Old Tricks, Anal. Chem. 2005, 77, 294A-302A.

Awards and Recognition

  • 2004 - University of Vermont University Scholar
  • 2007 - Member, Vermont Academy of Science and Engineering
  • 2014 - Pomeroy Professor of Chemistry, University of Vermont

Areas of Expertise and/or Research

analytical chemistry, mass spectrometry, proteomics

Education

  • Ph.D., Indiana University, 1977

Contact

Phone:
  • (802) 656-8114
Office Location:

Discovery W322