The application of nuclear magnetic resonance (NMR) as a tool for measuring intermediary metabolism depends upon high NMR sensitivity for carbon-13 and deuterium nuclei. The sensitivity is governed by the applied magnetic field strength and the efficiency of the detection circuit. Recent data acquired using dynamic nuclear polarization (DNP) to enhance the magnetic resonance signal shows an increase in signal to noise of a factor of 10000 or more. Sensitivities of this magnitude would fundamentally change the types of problems we can approach with stable isotope methods. We are beginning a research program focused on using DNP for NMR analysis of metabolism. Metabolomics is the use of any analytical technique to take a global snapshot of the metabolism of a living system. NMR is an excellent tool for metabolomics, but the data reduction needed for an NMR spectrum of even 25 small molecule metabolites demands the development of new algorithms that can robustly establish differences between samples. Currently, we are developing a peak-finding partial least squares method for analyzing proton NMR spectra, both ex and in vivo. The application of this technology will increase our understanding of a variety of pathological states, including diabetes and cancer.
RESEARCH INTERESTS
Magnetic Resonance
Hyperpolarization for NMR sensitivity enhancement
Metabolomics and Efficient NMR Data Reduction
RECENT PUBLICATIONS
Hausler, N., Browning, J., Merrit, M., Storey, C., Milde, A., Jeffrey, FMH., Sherry, A. D., Malloy, C., Burgess, S., "Effects of insulin and cytosolic redox state on glucose production pathways in the isolated perfused mouse liver measured by integrated 2H and 13C NMR." Biochemical Journal, 394(2):465-473, 2006
Jin, E., Jones, J., Merritt, M., Burgess, S., Malloy, C., Sherry, A.D., "Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative." Analytical Biochemistry, 327(2):149-155, 2004
SIGNIFICANT PUBLICATIONS
Matthew E. Merritt, Shawn C. Burgess, Timothy D. Spitzer, "Adiabatic JHSQC for 13C isotopomer analysis" Magnetic Resonance in Chemistry, 44(4):463-466, 2006
Merritt, M., Bretthorst, GL., Burgess, S., Jeffrey, FMH., Sherry, AD., Malloy, C.,, "TCA cycle turnover and serum glucose sources by automated Bayesian analysis of NMR spectra." Magnetic Resonance in Medicine, 50(4):659-663, 2003
Woessner, D., Zhang, S., Merritt, M., Sherry, A. D., "Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI." Magnetic Resonance in Medicine, 53(4):790-799, 2005
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