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Clinical Pharmacology
Clinical Pharmacology

The practice of medicine is an art, not a trade, a calling, not a business, a calling in which your heart will be exercised equally with your head.
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Dwight Matthews' Laboratory

Our research focuses on analytical chemistry and metabolism/nutrition.

Research Foci

 

Research in Analytical Chemistry

Research in Metabolism and Nutrition

 
Research in Analytical Chemistry

Dr. Dwight Matthews leads a group of researchers who have used 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 stable isotopes in biological molecules and mathematical and computer models to interpret the stable isotope tracer kinetic data obtained from biological samples.
 
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.  We do not know which pathways regulate the metabolism of several important amino acids in humans.

We do not know how protein and amino acid metabolism is regulated in the body to maintain protein stores or why the body accelerates oxidation of amino acids in states of stress, trauma, or sepsis using protein stores to the point of being life threatening.

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, liquid chromatography-mass spectrometry, and isotope ratio mass spectrometry instrumentation are all available and are used for research in our group to measure stable isotope ratio tracers in biological samples.

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Research in Metabolism and Nutrition

Dr. Richard Galbraith leads a group of researchers who have used stable isotopically labeled tracers and kinetic models to measure rates and flows of individual metabolites in vivo in the human body.  These kinetic data are then used to define human physiology and relate physiology to nutritional needs of humans.

Over the past two decades we have developed a variety of tracer methods for measuring most of the amino acids and their metabolism in the body.

  1. One of the earliest and most widely applied methods we have developed was the use of [1-13C]leucine and similar essential amino acid tracers to follow in vivo rates of whole body protein breakdown, oxidation, and uptake of amino acids for protein synthesis.  Most of this early work was performed at Washington University School of Medicine in St. Louis with Dennis Bier, M.D. and with Vernon Young, Ph.D. at MIT in Boston.
     

  2. A second area of research is to understand how specific hormones regulate and alter amino acid and protein metabolism.  Protein is absolutely critical for life.  It forms the basis of skeletal muscle that provides the structure for our mobility, our ability to breath and our ability to pump blood through the heart.  Protein is the heart of our immune function and the heart of all enzymes that make it possible for all of the chemistry of life to occur.  When people die of starvation, they generally do not die of lack of fuel, but of a loss of protein.  Lose much more than 25% of your protein, and the critical functions of life will cease.  The body regulates and conserves protein stores to maintain protein mass as best as possible.  Yet in injury and stress, the body uses protein for energy at an accelerated rate.  We have been studying how individual hormones contribute to this process and have addressed control of protein metabolism by individual hormones.

  3. A third area of research involves understanding the digestion and distribution of individual amino acids.  Protein cannot be made unless all 20 amino acids are present in appropriate amounts.  If any amino acid is lacking, protein synthesis will be impaired.  In addition, amino acids play key roles as precursors for a variety of other compounds and factors in the body. 

    The least understood area of metabolism is the metabolism of the nonessential amino acids. Because these amino acids can be produced in the body, they are not essential to our diet.

    However, that does not mean they are not important.  These amino acids have numerous pathways of importance in the body, yet we have a poor understanding of which pathways are prominent or how these pathways are regulated in specific organs.  We have been studying how key nonessential amino acids are metabolized by the gut and liver when given in the diet.

  4. A fourth area of research involves the regulation of protein stores, specifically skeletal muscle metabolism.  Besides being the largest reservoir of protein in the body, muscle protein is critical to our mobility.  A lack of muscle protein means a lack of strength and increased disability.  We know that people lose muscle mass and strength with advancing age.  We know that women lose muscle mass faster after menopause, but we do not understand why these losses occur.  We are applying methods of stable isotopes to measure directly the rate of synthesis of muscle protein.  We are interested in understanding both what happens to the synthesis of muscle as women go through menopause and how we can best maintain synthesis of muscle protein in postmenopausal women.
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