Our goal is to understand the fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to devise novel therapies based on these discoveries. We approach this multidisciplinary problem with a wide range of techniques -- physiology, enzyme kinetics, molecular genetics, peptide synthesis, computer simulation -- but our forte is site-directed spectroscopic probes. After attaching site-directed probes (spin labels, fluorescent dyes, phosphorescent dyes, or isotopes) to selected muscle proteins in solution or in cells, we perform magnetic resonance or optical spectroscopy to directly detect the motions of the force-generating proteins, actin and myosin, or the membrane ion pumps and channels responsible for muscle excitation and relaxation. These same tools are then used to test the efficacy of gene or drug therapies designed to treat heart failure or muscular dystrophy.
McCarthy, MR, AR Thompson, F Nitu, RJ Moen, JC Klein, and DD Thomas. 2015. Impact of methionine oxidation on calmodulin structural dynamics. Biochem Biophys Res Commun 456:567-572.
Colson, BA, Petersen, KJ, Collins, BC, Lowe, DA, Thomas, DD. 2015. The myosin super-relaxed state is regulated by estradiol, Biochem Biophys Res Commun 456:151-155.
Ablorh, NA and DD Thomas. 2015. Phospholamban phosphorylation, mutation, and structural dynamics: a biophysical approach to understanding and treating cardiomyopathy. Biophys Rev 7:63-76.
Petersen, KJ, KC Peterson, JM Muretta, SE Higgins, GD Gillispie, and DD Thomas. 2014. Fluorescence lifetime plate reader: resolution and precision meet high-throughput. Rev Sci Instrum 81:113101-113107.
McCaffrey, JE, ZM James, and DD Thomas. 2014. Optimization of bicelle lipid composition and temperature for EPR spectroscopy of aligned membranes. J Mag Res 250:71-75.
Moen, RJ, S Cornea, DE Oseid, BP Binder, JC Klein, and DD Thomas. 2014. Redox-sensitive residue in myosin II actin-binding interface. Biochem Biophys Res Commun 453:345-349.
Svensson, B, T Oda, FR Nitu, Y Yang, I Cornea, Y Chen-Izu, JD Fessenden, DM Bers, DD Thomas, and RL Cornea. 2014. FRET-based trilateration of probes bound within functional ryanodine receptors. Biophys J 107:2037-2048.
Ablorh, N-A, X Dong, ZM James, Q Xiong, J Zhang, DD Thomas, and CB Karim. 2014. Synthetic phosphopeptides enable quantitation of the content and function of phospholamban’s four phosphorylation states in cardiac muscle. J Biol Chem 289:29397-29405.
Espinoza-Fonseca, LM, BA Colson, and DD Thomas. 2014. Effects of pseudophosphorylation mutants on the structural dynamics of smooth muscle myosin regulatory light chain. Mol Biosys 10:2693-2698.
Mahalingam, M, T Girgenrath, B Svensson, DD Thomas, RL Cornea,* and JD Fessenden.* 2014. Structural mapping of divergent regions in the type 1 ryanodine receptor using fluorescence resonance energy transfer. Structure, 22:1322-1332. *co-senior authors.