Thomas James

Research Interests

Our research predominantly entails use of nuclear magnetic resonance. Most of our current effort involves use of high-resolution NMR to study biomolecular structure and dynamics, as well as for drug discovery.

A rather different aspect of exploiting the versatility of the magnetic resonance phenomenon has been applied to in vivo studies. For example, we have been successful in development of molecular signals for in vivo monitoring of effects caused by toxic agents. Specifically we have been developing a means of following glutathione in rat liver in situ using NMR; we can simultaneously follow other markers of intracellular pH and bioenergetics with the radiofrequency coil developed for these studies. We have also successfully demonstrated a bioreactor for use in NMR spectrometers; with further development, the bioreactor containing hepatocytes could prove to be a useful toxicology tool as well.

Research Summary

Overarching goals of our research are (a) to improve the capability for determining dynamic structures of proteins and nucleic acids, i.e., include conformational flexibility in structural descriptions, (b) apply that methodology to the study of small molecule-macromolecule interactions and RNA/protein systems, and (c) use three-dimensional RNA structures and computational search algorithms to discover novel ligands that can serve as lead compounds for drug discovery. Core to this work are multidimensional NMR experiments and calculations.

Selected Publications

J.M. Macdonald, O. Schmidlin and T.L. James. In Vivo Monitoring of Hepatic Glutathione in Anesthetized Rats by 13C NMR. Magn. Reson. Med. 48, 430-439 (2002).

J. Zeng, G.-Y. Yang, W. Ying, M. Kelly, K. Hirai, T.L. James, R.A. Swanson, and L. Litt, Pyruvate Improves Recovery after PARP-1 Associated Energy Failure Induced by Oxidative Stress in Neonatal Rat Cerebrocortical Slices.  J. Cerebral Blood Flow Metab.,publ. on-line 24 May (2006).

M. Mayer, P.T. Lang, S. Gerber, P.B. Madrid, I. Gómez Pinto, R.K. Guy and T.L. James. Synthesis and Testing of a Focused Phenothiazine Library for Binding to HIV-1 TAR RNA. Chemistry & Biology 13, 993-1000 (2006).

N.B. Ulyanov, A. Mujeeb, Z. Du, M. Tonelli, T.G. Parslow and T.L.James, NMR Structure of the Full-Length Linear Dimer of Stem-Loop-1 RNA in the HIV-1 Dimer Initiation Site. J. Biol. Chem., 281, 16168-16177 (2006).

Z. Du, J.K. Lee, R. Tjhen, S. Li, H. Pan, R.M. Stroud and T.L. James. Crystal Structure of the First KH Domain of Human Poly(C)-Binding Protein-2 in Complex with a C-Rich Strand of Human Telomeric DNA at 1.7 Å. J. Biol. Chem. 280, 38823-38830 (2005).