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.
Rohde, JA, DD Thomas*, and JM Muretta*. 2017. Heart failure drug changes the mechanoenzymology of the cardiac myosin powerstroke. Proc Nat Acad Sci USA 114:E1796-E1804. PMC5347578.
Schaaf, TM, KC Peterson, BD Grant , P Bawaskar, S Yuen, J Li, JM Muretta, GD Gillispie, and DD Thomas. 2017. High-throughput spectral and lifetime-based FRET screening in living cells to identify small molecule effectors of SERCA. SLAS Discov 22:262-273. PMC5323330
Schaaf, TM, KC Peterson, BD Grant, DD Thomas, and GD Gillispie. 2017. Spectral unmixing plate reader: high-throughput, high-precision FRET assays in living cells. SLAS Discov 22:250-261. PMC5323330.
Bian, T, JM Autry, D Casemore, J Li, DD Thomas, G He, and C Xing. 2016. Direct detection of SERCA calcium transport and small-molecule inhibition in giant unilamellar vesicles. Biochem Biophys Res Commun 481:206–211. PMC5123963.
Autry, JM, DD Thomas, and LM Espinoza-Fonseca. 2016. Sarcolipin promotes uncoupling of the SERCA Ca2+ pump by inducing a structural rearrangement in the energy-transduction domain. Biochemistry 55:6083–6086. (Rapid Report)..
Her, C, JE McCaffrey, DD Thomas*, and CB Karim*. 2016. Calcium-dependent structural dynamics of a spin-labeled ryanodine receptor peptide bound to calmodulin. Biophys J 111:2387-2394. PMC5154373.
Kraft, TE, MR Heitmeier, M Putanko, RL Edward, MXG Ilagan, MA Payne, JM Autry, DD Thomas, AR Odom, and PW Hruz. 2016. A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters. Antimicrob Agents Chemother 60:7007-7014. PMC5119023
Rebbeck, RT, MM Essawy, FR Nitu, DD Thomas, DM Bers, and RL Cornea. 2017. High-throughput screens to discover small molecule modulators of ryanodine receptor calcium release channels. J Biomol Screen 22: 176-186. PMC5337111.
Swanson, CJ, RF Sommese, KJ Petersen, M Ritt, J Karslake, DD Thomas, and S Sivaramakrishnan. 2016. Calcium stimulates self-assembly of protein kinase C α in vitro. PLOS ONE 11(10): e0162331. PMC5051681.
Lewis AK, K Dunleavy, TL Senkow, C Her, BT Horn, MA Jersett, R Mahling, MR McCarthy, GT Perell, CC Valley, CB Karim, J Gao, WC Pomerantz, DD Thomas, A Cembran, A Hinderliter, and JN Sachs. 2016. Oxidation increases the strength of the methionine-aromatic interaction. Nature Chem Biol 12:860-866. PMC5060120.