Shown in the background is beautiful Mt. Mansfield behind the University of Vermont (lovingly known as UVM). The water tower forms a landmark for directions to other buildings on campus.
Dr. Matthews is a Professor & Chairman of Chemistry in the College of Arts & Sciences and a Professor of Medicine in the College of Medicine. Information about Dr. Matthews and his research group can be found in the links on the left.
The proteomics facilities at UVM originate from Dr. Matthews laboratory. Proteomics takes several forms.For information about the proteomics facility at UVM, please go to the Vermont Genetics Network link.
What do we do?
We use mass spectrometry to measure stable isotopically labeled compounds. With these compounds we study metabolism in humans.
We also use mass spectrometry to measure peptides and proteins in the area of proteomics.
Stable isotopes are not radioactive, and they occur naturally in nature.
For example, 99% of all carbon in the world is carbon-12 (12C) and 1% is carbon-13 (13C). We purchase enriched stable isotopes that have been placed into compounds in abundances much greater than their natural abundance. We can obtain labeled compounds with ~95-99% 13C.
Because a mass spectrometer separates ions by mass, we use mass spectrometry to distinguish isotopes in compounds by their mass.
For example, 13C is 1 Dalton (or atomic mass unit) heavier than 12C, and a 13C-labelled compound appears in the mass spectrometer at a higher mass from an unlabeled compound.
We typically use the isotopes of hydrogen [protium (1H) and deuterium (2H)], nitrogen (14N and 15N) and oxygen (16O, 17O, & 18O).
We have a range of instruments (see link on left):
Liquid chromatograph mass spectrometers (LCMS) for proteomics work.
Gas chromatograph mass spectrometers (GCMS) for metabolite measurements.
Hybrid isotope ratio mass spectrometers (IRMS) with continuous flow inlets and either combustion interfaces between the GC and the IRMS (GC-C-IRMS) or pyrolysis interfaces between the GC and the IRMS (GC-P-IRMS). Dr. Matthews constructed and tested the first GC-C-IRMS instrument for measuring 13C & 15N in biological compounds.
We administer stable isotopically labeled compounds to humans as tracers to define the rates of production, disposal and conversion of metabolites in the body.
Using tracers we can determine, for example, how much glucose the liver is making at any point in time, how much protein is being broken down in the body and how much of each amino acid is being released from this breakdown.
We can tell whether the amino acids released from protein breakdown are reused for synthesis into new protein or are oxidized to CO2 by measuring the 13CO2 enrichment in a person's breath after a 13C-labelled tracer amino acid has been infused.
We can use tracers and mass spectrometers to study specific metabolomes.
We use mass spectrometry to identify proteins and their modifications, and we use stable isotopes to quantify protein and peptide amounts in proteomics.
Measuring stable isotopic enrichments in biological compounds is not simple:
Mass spectrometry instrumentation comes in different forms—all expensive and complex to use.
In most cases, biological samples require isolation and modification steps before they are suitable for measurement by mass spectrometry.
Designing experiments and labeled compounds to measure a specific metabolic event in the body is not simple.
As analytical chemists,
We develop new techniques in mass spectrometry to measure stable isotopically labeled compounds in humans in new, more precise, and more sensitive ways.
We develop new methods of sample isolation and derivatization.
We develop kinetic models to understand tracer metabolism in the body.
We develop mass spectrometry methods for proteomics.
As clinical scientists in medicine,
We study how amino acid, glucose, and fat metabolism are regulated in humans.
We study how hormones regulate metabolism.
We study how metabolism is altered in different metabolic diseases, such as obesity and diabetes.
We are interested in nutrition and how the gut and liver metabolize dietary amino acids.
We are interested in metabolic changes with aging.